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Expert discusses which diets are best, based on the evidence
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
AT INTERNAL MEDICINE 2023
Adherence to cancer prevention guidance linked with reduced breast cancer recurrence, death risk
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
FROM JAMA NETWORK OPEN
Cancer pain declines with cannabis use
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
FROM BMJ SUPPORTIVE & PALLIATIVE CARE
The next big thing in cancer research
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM CELL
Antibody Drug Conjugates: a growing field of targeted therapy for breast cancer
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
Commentary: Surgical, Tamoxifen, and Genetic Considerations in Breast Cancer, May 2023
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
Commentary: Endocrine therapy and mammography, May 2023
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017
Guidelines for assessing cancer risk may need updating
The authors of the clinical trial suggest that these guidelines may need to be revised.
Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.
The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.
“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.
Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.
“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.
She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.
The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.
Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.
“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.
Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.
“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.
The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.
Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.
During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.
Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.
“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.
Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.
The authors of the clinical trial suggest that these guidelines may need to be revised.
Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.
The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.
“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.
Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.
“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.
She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.
The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.
Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.
“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.
Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.
“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.
The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.
Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.
During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.
Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.
“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.
Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.
The authors of the clinical trial suggest that these guidelines may need to be revised.
Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.
The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.
“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.
Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.
“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.
She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.
The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.
Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.
“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.
Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.
“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.
The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.
Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.
During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.
Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.
“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.
Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.
FROM AACR 2023
Evaluating patients with breast concerns: Lump, pain, and mastitis
The vast majority of symptomatic breast conditions are benign, with the most common symptoms being palpable mass and breast pain. Clinicians, including primary care clinicians and gynecologists, play a crucial role by performing the initial assessment and subsequent therapies and referrals and serve as the mediator between the specialists and by being the patient’s spokesperson. It is therefore important for clinicians to be aware of the various possible causes of these breast symptoms, to know which imaging tests to order, and also to understand the indications for biopsies and surgical referral.
Common types of breast lumps: Imaging workup and management
Accounting for 8% of women who present with breast symptoms, breast lump is the second most common symptom after breast pain.1 The positive likelihood ratio of finding breast cancer is highest among women with breast lumps compared with any other breast symptoms. Therefore, anxiety is related to this symptom, and a thorough evaluation is recommended.1 Cysts, fibroadenoma, and fat necrosis are 3 common benign causes of breast lumps.2
In this section, we review clinical presentation, imaging workup, and management strategies for common types of breast lumps.
CASE 1 Woman with tender breast lump
A 45-year-old woman presents with a breast lump of 6 months’ duration that is associated with a change in size with the menstrual cycle and pain. Clinical examination reveals a 4 x 4.5–cm mass in the right breast in the retroareolar region, which is smooth with some tenderness on palpation.
Breast cyst
According to the American College of Radiology appropriateness criteria for an adult woman 40 years of age or older who presents with a palpable breast mass, the initial imaging study is diagnostic mammography with or without digital tomosynthesis, usually followed by a directed ultrasound. If the mammogram is suspicious or highly suggestive of malignancy, or in cases where the mammogram does not show an abnormality, the next recommended step is breast ultrasonography. Any suspicious findings on ultrasound or mammogram should be followed by an image guided biopsy. Ultrasonography also may be appropriate if the mammogram findings are benign or probably benign.
For an adult woman younger than age 30 who presents with a palpable breast mass, breast ultrasonography is the appropriate initial imaging study. If the ultrasound is suspicious or highly suggestive of malignancy, then performing diagnostic mammography with or without digital tomosynthesis or ultrasound-guided core needle biopsy of the mass are both considered appropriate. However, no further imaging is recommended if the ultrasound is benign, probably benign, or negative. Breast ultrasonography or mammography is appropriate as the initial imaging test for adult women aged 30 to 39 years who present with a palpable breast mass.3,4
Approximately 50% of women after age 30 may develop fibrocystic breast disease, and 20% of them can present with pain or lump due to a macrocysts. Simple cysts must be distinguished from complex cysts with the help of ultrasound as the latter are associated with 23% to 31% increased risk of malignancy.
In this 45-year-old patient, the initial mammogram demonstrated a circumscribed mass underneath the area of palpable concern (FIGURE 1a, 1b). Targeted breast ultrasonography was performed for further assessment, which depicted the mass as a benign simple cyst (FIGURE 1c).
On ultrasound, a simple cyst is an anechoic, well-circumscribed mass with a thin capsule and with increased through transmission. Patients with small and asymptomatic simple cysts do not need imaging follow-up and can return for routine screening mammograms.
A breast surgeon, radiologist, or gynecologist can perform percutaneous aspiration if a cyst is large and symptomatic. A cyst with low-level internal echoes, fluid-fluid, or fluid-debris levels is considered a complicated cyst. Differential diagnosis also includes hematoma, fat necrosis, abscess, and galactocele, depending on the clinical presentation. Fine-needle aspiration or short-interval follow-up5,6 is appropriate for complicated cysts, while incision and drainage is indicated in patients with infected cysts and abscesses. A cyst with a solid component is considered a cystic, solid mass, and core needle biopsy is recommended. The differential diagnosis for cysts with solid components includes intracystic papilloma, papillary carcinoma, ductal carcinoma in situ, and necrotic cancers.5,6
Continue to: CASE 2 Painless breast mass in a young woman...
CASE 2 Painless breast mass in a young woman
A 22-year-old woman presents with a 2-month history of breast lump, which is not associated with pain or nipple discharge. On examination, there is a 2 x 2–cm mass in the right breast at 12 o’clock, 2 cm from the nipple, which is mobile, smooth, and nontender on palpation.
Fibroadenoma
In this 22-year-old, the initial imaging of choice is breast ultrasonography. Breast ultrasonography can differentiate a cystic mass from a solid mass, and it does not involve radiation. Right breast targeted ultrasound showed a circumscribed oval homogeneous hypoechoic mass that is wider than tall (FIGURE 2). The patient desired surgical removal, and a pre-lumpectomy core needle biopsy revealed a fibroadenoma.
Fibroadenoma is the most common benign tumor of the breast. It is most often encountered in premenopausal women. Patients present with a painless breast lump, which is smooth and mobile on palpation. Fibroadenoma can be followed expectantly with repeat ultrasound (to assess over time for growth) if it is small and asymptomatic. No further action is needed if it remains stable. If a patient desires surgical excision, a core needle biopsy is usually performed before lumpectomy.
Excisional biopsy or removal of the mass is recommended if the mass is greater than 3 or 4 cm, is symptomatic, or if there is an increase in size that raises clinical concern for phyllodes tumor. Imaging features that are concerning for phyllodes tumors are size greater than 3 cm, indistinct or microlobulated margins, and heterogeneous echo pattern.7,8 In cases in which the imaging features are concerning for phyllodes tumor and a core needle biopsy is not definitive, wide surgical excision is recommended for definitive diagnosis.8
CASE 3 Patient develops breast mass post-surgery
A 45-year-old woman presents with a tender left breast mass that she noticed 2 months after breast reduction surgery. It has been increasing in size since. On clinical examination, a 4 x 4–cm mass is found at the surgical scar site, which is indurated on palpation and tender.
Fat necrosis
In this 45-year-old, the initial test of choice is diagnostic mammography, which showed a somewhat circumscribed area with fat under the palpable marker (FIGURE 3a). Breast ultrasonography was performed for further evaluation, which was inconclusive as the ultrasound showed ill-defined areas of mixed echogenicity (FIGURE 3b). Breast magnetic resonance imaging (MRI) clearly demonstrated fat necrosis in the area of the palpable lump (FIGURE 3c).
Fat necrosis of the breast is an inflammatory process that is seen after breast trauma or surgery. It can present as an incidental mammogram finding or a palpable mass. The patient may give a history of trauma, breast reduction surgery, or breast cancer surgery followed by radiation treatment. On clinical examination, fat necrosis occasionally can present as a firm mass with skin retraction or swelling concerning for cancer. Imaging features are variable depending on the stage of fat necrosis and inflammation.9-11
A mammogram may demonstrate a circumscribed fat-containing mass, an ill-defined mass, asymmetry or calcified oil cyst, and dystrophic calcifications. On ultrasound, fat necrosis can appear as anechoic or hypoechoic or as a complicated cyst or a mixed cystic, solid mass. MRI demonstrates a circumscribed or irregular fat-containing mass, with or without enhancement, and architectural distortion.
When the imaging features are clearly benign—for example, a circumscribed fat-containing mass on mammogram or on ultrasound or, on MRI, marked hypointensity of fat in the center of a circumscribed mass when compared with surrounding fat (keyhole sign)—no further follow-up is needed. When the imaging features are indeterminate, however, a short-interval follow-up can be considered. In cases with irregular fat-containing mass with enhancement, core needle biopsy is indicated to exclude cancer. If the workup remains inconclusive and the level of clinical suspicion is high, surgical excision can be performed for a definitive diagnosis.12
Continue to: Investigating breast pain: Imaging workup and management...
Investigating breast pain: Imaging workup and management
Breast pain, or mastalgia, is the most common concern of women presenting to a breast clinic and accounts for approximately half of such encounters.13 Causes of breast pain include hormonal changes, fibrocystic changes, musculoskeletal causes (such as costochondritis), lack of support, infection, and injury. While mastalgia often causes patient concern, the risk of malignancy in a woman presenting with breast pain alone is low. Still, it is essential to rule out other findings suspicious for cancer (mass, skin changes, or nipple discharge) with a thorough history and breast examination.
In this section, we review clinical presentation, imaging workup, and management for breast pain.
CASE 4 Woman with noncyclic breast pain
A 26-year-old woman presents to the clinic with mastalgia. The pain is noncyclic and primarily located in the upper outer quadrant of her left breast. There is no history of breast cancer in her family. She has no suspicious findings on the breast examination.
Mastalgia
The test of choice for this 26-year-old with focal left breast pain is targeted breast ultrasound. The patient’s ultrasound image showed no suspicious findings or solid or cystic mass (FIGURE 4).
Two important characteristics of breast pain are whether it is noncyclical and whether it is focal. According to the American College of Radiology, no breast imaging is recommended for clinically insignificant cyclical, nonfocal (greater than 1 quadrant)/diffuse pain, as this type of mastalgia is not associated with malignancy.14
For patients age 40 or older, if they are not up to date with their annual screening mammogram, then a mammogram should be performed. An imaging workup is warranted for clinically significant mastalgia that is noncyclical and focal. Even then, no malignancy is identified in most patients with clinically significant mastalgia; in patients with breast pain as their only symptom, the prevalence of breast cancer is 0% to 3.0%.15-19
The initial imaging modality differs by patient age: younger than 30 years, ultrasonography; between 30 and 40 years, mammography or ultrasonography; and older than 40 years, mammography first followed by ultrasonography.14
Treatment of breast pain is primarily symptomatic, and evidence for specific treatments is generally lacking. Cyclical breast pain resolves spontaneously in 20% to 30% of women, while noncyclical pain responds poorly to treatment but resolves spontaneously in half of women.20 Reassurance is important and wearing a supportive bra often can alleviate breast pain. In addition, reducing caffeine intake can be helpful.
As a first-line treatment, both topical (diclofenac) and oral nonsteroidal anti-inflammatory drugs effectively can relieve breast pain. Supplements and herbal remedies (for example, evening primrose oil, vitamin E, flaxseed) have varying effectiveness and are of questionable benefit as few have trials to support their effectiveness.4 Danazol and tamoxifen have been shown to have some benefits but they also have adverse effects.20 Surgery does not play a role in the treatment of mastalgia.
CASE 5 Breastfeeding woman with breast pain
A 27-year-old postpartum woman presents with concerns for redness and pain in the upper inner left breast. She has been breastfeeding for the past few months. Breast examination demonstrates a 5-cm area of erythema and warmth but no fluctuance or masses.
Lactational mastitis
Targeted ultrasonography is the test of choice for this 27-year-old patient with focal breast pain, and the imaging revealed edema of subcutaneous tissues and ill-defined hypoechoic areas, likely inflamed fat lobules (FIGURE 5). These findings suggest uncomplicated lactational mastitis, which can be treated with antibiotics. Generally, the mastitis will improve within days of starting the antibiotics; if it does not improve, repeat examination and ultrasound should be performed to look for formation of an abscess that may require aspiration.
Continue to: CASE 6 Woman with painful periareolar mass...
CASE 6 Woman with painful periareolar mass
A 42-year-old perimenopausal woman describes having pain near the nipple of her right breast. She is a smoker and has no history of breast cancer in her family. Examination demonstrates a palpable, erythematous, painful, 3-cm periareolar fluctuant mass.
Nonpuerperal periareolar abscess
Appropriate initial imaging for this 42-year-old patient with focal pain is a diagnostic mammogram, which showed skin thickening and a retroareolar mass (FIGURE 6a). Further evaluation with targeted ultrasound showed a thick-walled anechoic collection with echoes compatible with an abscess (FIGURE 6b).
Mammographic findings in a patient with mastitis may be normal or demonstrate skin and trabecular thickening. Ultrasound imaging may show dilated ducts and heterogeneous tissue secondary to inflammation and edema without a discrete fluid collection. In cases with breast abscess, in addition to the mammographic findings described above, a mass, or an asymmetry, may be seen, most commonly in a subareolar location. On ultrasound, a hypoechoic collection with mobile debris, no internal flow on Doppler, and thick hypervascular walls can be seen with abscess, occasionally giving the appearance of a complicated cyst or a mixed cystic, solid mass.
The most important differential for mastitis is inflammatory breast cancer. Most cancers appear solid but can have central necrosis, mimicking a complicated cystic mass on ultrasound. The location for mastitis or abscess is most frequently subareolar. The presence of microcalcifications in a mass indicates the possibility of cancer.
Contrast-enhanced MRI can be helpful to differentiate between infection and cancer, with cancers showing initial early enhancement and washout kinetics compared with infected collections that show no enhancement or peripheral enhancement with a plateau or persistent enhancement curves. When clinical and imaging findings are unchanged after treatment of mastitis and abscesses, a core needle biopsy should be performed.21,22
There are 2 categories of mastitis and breast abscess: lactational and nonpuerperal (all mastitis that occurs outside the lactational period). The World Health Organization definition of puerperal mastitis includes pain, local redness, warmth and swelling of the breast (usually unilateral), fever, and malaise.4 Concerning etiology, epithelial lesions in the nipple area caused by breastfeeding can allow pathogens to enter and cause infection. The most common microorganism is Staphylococcus aureus.4 Continued emptying of the breast is important, combined with early antibiotic therapy (dicloxacillin is often the first line; if the patient is penicillin allergic, use a macrolide such as clindamycin). If no improvement is seen in 48 to 72 hours, imaging should be performed.
In most cases, continuation of breastfeeding is possible. If mastitis has evolved into an abscess in a lactating woman, it can be aspirated under ultrasound guidance. Incision and drainage should be avoided unless the abscess persists after multiple aspiration attempts, it is large, or if the overlying skin is thin or otherwise appears nonviable.
Nonpuerperal mastitis includes peripheral, periductal, and idiopathic granulomatous mastitis (IGM). Peripheral mastitis behaves like infections/abscesses in other soft tissues, responds well to treatment (antibiotics and percutaneous drainage), and is less likely to recur than periductal mastitis and IGM.21,23
Periductal mastitis and abscess, also known as Zuska disease, has a pathogenesis distinct from other forms of mastitis. Squamous metaplasia of the usual cuboidal epithelium of the breast ducts leads to keratin plugging that can cause infection.23 Risk factors include obesity, smoking, and macromastia. The typical presentation of Zuska disease is a woman with a history of chronic smoking and/or a congenital cleft in the central nipple.23 Periareolar signs of inflammation (redness, swelling, warmth) may be accompanied by an abscess. These can recur and lead to chronic fistula formation, especially if there is a history of intervention (such as aspiration, incision, and drainage).
Treatment of Zuska disease includes symptom relief and antibiotics. If S aureus is present, infection with methicillin-resistant S aureus is likely, and treatment with clindamycin or amoxicillin/clavulanic acid is preferred. If abscess is present, aspiration (preferred, often under ultrasound guidance) or incision and drainage (if the skin is compromised) may be required. If disease is recurrent or associated with a chronically draining fistula, surgical intervention may be warranted, in which resolution requires removing the keratin-plugged ducts in and immediately below the central core of the nipple. Given the association between Zuska disease and smoking, cessation should be encouraged, although there is no guarantee that this will resolve the issue.23
Continue to: CASE 7 Patient with breast pain and swelling...
CASE 7 Patient with breast pain and swelling
A 39-year-old woman presents with left breast swelling and pain of 1 month’s duration. On examination, there is a 6-cm area of edema, induration, and erythema.
Granulomatous mastitis
A diagnostic mammogram and ultrasound demonstrated an ill-defined hypoechoic mass (FIGURE 7a). Ultrasound-guided biopsy was performed, which showed granulomatous mastitis, negative for fungus and acid-fast bacilli. The patient was treated with prednisone and gradually improved (FIGURE 7b).
Granulomatous mastitis (GM) is a rare benign inflammatory process, with etiologies that include fungal infections, tuberculosis, Wegener granulomatosis, sarcoidosis, and idiopathic causes. Imaging can be nonspecific and show variable features. Mammograms can appear normal or show asymmetry or mass and skin thickening. Ultrasound can show heterogeneous parenchyma, ill-defined hypoechoic collection, or a mass with margins that can be circumscribed or indistinct or with tubular extensions, with or without overlying skin thickening, fistulas, and reactive lymph nodes.24
In this clinical setting, the differential diagnosis includes infectious mastitis, inflammatory breast cancer, foreign body injection granulomas, and diabetic mastopathy. Treatment involves drainage and fluid culture if there is a collection on imaging. A core biopsy is performed if imaging demonstrates a solid mass or fluid culture is negative and symptoms persist or recur. Oral steroids represent the mainstay of treatment if a core biopsy shows GM. However, immunosuppressants, including methotrexate, and surgery are options if initial treatment is not helpful.25,26
Conclusion
Breast symptoms are common reasons for patient visits to obstetricians and gynecologists. With a good understanding of the various symptomatic breast diseases and conditions, and by having a close collaboration with radiologists and breast surgeons, clinicians can provide excellent care to these patients and thereby improve patient outcomes and satisfaction. ●
- Eberl MM, Phillips RL Jr, Lamberts H, et al. Characterizing breast symptoms in family practice. Ann Fam Med. 2008;6:528-533.
- Malherbe F, Nel D, Molabe H, et al. Palpable breast lumps: an age-based approach to evaluation and diagnosis. S Afr Fam Pract (2022). 2022;64:e1-e5.
- Expert Panel on Breast Imaging; Klein KA, Kocher M, Lourenco AP, et al. American College of Radiology ACR appropriateness criteria: palpable breast masses. Accessed February 15, 2023. https://acsearch.acr.org/docs/69495/Narrative/
- Stachs A, Stubert J, Reimer T, et al. Benign breast disease in women. Dtsch Arztebl Int. 2019;116:565574.
- Hines N, Slanetz PJ, Eisenberg RL. Cystic masses of the breast. AJR Am J Roentgenol. 2010;194:W122133.
- Berg WA. Reducing unnecessary biopsy and follow-up of benign cystic breast lesions. Radiology. 2020;295:52-53.
- Duman L, Gezer NS, Balcı P, et al. Differentiation between phyllodes tumors and fibroadenomas based on mammographic sonographic and MRI features. Breast Care. 2016;11:123-127.
- Lerwill MF, Lee AHS, Tan PH. Fibroepithelial tumours of the breast—a review. Virchows Arch. 2022;480:45-63.
- Vasei N, Shishegar A, Ghalkhani F, et al. Fat necrosis in the breast: a systematic review of clinical. Lipids Health Dis. 2019;18:139.
- Kerridge WD, Kryvenko ON, Thompson A, et al. Fat necrosis of the breast: a pictorial review of the mammographic, ultrasound, CT, and MRI findings with histopathologic correlation. Radiol Res Pract. 2015;2015:613139.
- Taboada JL, Stephens TW, Krishnamurthy S, et al. The many faces of fat necrosis in the breast. AJR Am J Roentgenol. 2009;192:815-825.
- Tan PH, Lai LM, Carrington EV, et al. Fat necrosis of the breast—a review. Breast. 2006;15:313-318.
- Holbrook AI. Breast pain, a common grievance: guidance to radiologists. AJR Am J Roentgenol. 2020;214:259-264.
- Expert Panel on Breast Imaging; Moy L, Heller SL, Bailey L, et al. ACR appropriateness criteria: palpable breast masses. J Am Coll Radiol. 2017;14:S203-S224.
- Chetlen AL, Kapoor MM, Watts MR. Mastalgia: imaging workup appropriateness. Acad Radiol. 2017;24:345-349.
- Arslan M, Kucukerdem HS, Can H, et al. Retrospective analysis of women with only mastalgia. J Breast Health. 2016;12:151-154.
- Fariselli G, Lepera P, Viganotti G, et al. Localized mastalgia as presenting symptom in breast cancer. Eur J Surg Oncol. 1988;14:213-215.
- Leddy R, Irshad A, Zerwas E, et al. Role of breast ultrasound and mammography in evaluating patients presenting with focal breast pain in the absence of a palpable lump. Breast J. 2013;19:582-589.
- Leung JW, Kornguth PJ, Gotway MB. Utility of targeted sonography in the evaluation of focal breast pain. J Ultrasound Med. 2002;21:521-526.
- Goyal A. Breast pain. BMJ Clin Evid. 2011; 2011:0812.
- Kasales CJ, Han B, Smith Jr JS, et al. Nonpuerperal mastitis and subareolar abscess of the breast. AJR Am J Roentgenol. 2014;202:W133-W139.
- Mahoney MC, Ingram AD. Breast emergencies: types, imaging features, and management. AJR Am J Roentgenol. 2014;202:W390-W399.
- Snider HC. Management of mastitis, abscess, and fistula. Surg Clin North Am. 2022;102:1103-1116.
- Oztekin PS, Durhan G, Kosar PN, et al. Imaging findings in patients with granulomatous mastitis. Iran J Radiol. 2016;13:e33900.
- Pluguez-Turull CW, Nanyes JE, Quintero CJ, et al. Idiopathic granulomatous mastitis: manifestations at multimodality imaging and pitfalls. Radiographics. 2018;38:330-356.
- Hovanessian-Larsen LJ, Peyvandi B, Klipfel N, et al. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193:574-581.
Dr. Jasra is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
Dr. Sharma is Assistant Professor, Department of Radiology, University of Florida College of Medicine–Jacksonville.
Dr. Deladisma is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine–Jacksonville.
Dr. Neumayer is Professor and Chair, Department of Surgery, University of Florida College of Medicine–Jacksonville.
The authors report no financial relationships relevant to this article.
Dr. Jasra is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
Dr. Sharma is Assistant Professor, Department of Radiology, University of Florida College of Medicine–Jacksonville.
Dr. Deladisma is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine–Jacksonville.
Dr. Neumayer is Professor and Chair, Department of Surgery, University of Florida College of Medicine–Jacksonville.
The authors report no financial relationships relevant to this article.
Dr. Jasra is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
Dr. Sharma is Assistant Professor, Department of Radiology, University of Florida College of Medicine–Jacksonville.
Dr. Deladisma is Assistant Professor, Department of Surgery, Division of General Surgery, University of Florida College of Medicine–Jacksonville.
Dr. Neumayer is Professor and Chair, Department of Surgery, University of Florida College of Medicine–Jacksonville.
The authors report no financial relationships relevant to this article.
The vast majority of symptomatic breast conditions are benign, with the most common symptoms being palpable mass and breast pain. Clinicians, including primary care clinicians and gynecologists, play a crucial role by performing the initial assessment and subsequent therapies and referrals and serve as the mediator between the specialists and by being the patient’s spokesperson. It is therefore important for clinicians to be aware of the various possible causes of these breast symptoms, to know which imaging tests to order, and also to understand the indications for biopsies and surgical referral.
Common types of breast lumps: Imaging workup and management
Accounting for 8% of women who present with breast symptoms, breast lump is the second most common symptom after breast pain.1 The positive likelihood ratio of finding breast cancer is highest among women with breast lumps compared with any other breast symptoms. Therefore, anxiety is related to this symptom, and a thorough evaluation is recommended.1 Cysts, fibroadenoma, and fat necrosis are 3 common benign causes of breast lumps.2
In this section, we review clinical presentation, imaging workup, and management strategies for common types of breast lumps.
CASE 1 Woman with tender breast lump
A 45-year-old woman presents with a breast lump of 6 months’ duration that is associated with a change in size with the menstrual cycle and pain. Clinical examination reveals a 4 x 4.5–cm mass in the right breast in the retroareolar region, which is smooth with some tenderness on palpation.
Breast cyst
According to the American College of Radiology appropriateness criteria for an adult woman 40 years of age or older who presents with a palpable breast mass, the initial imaging study is diagnostic mammography with or without digital tomosynthesis, usually followed by a directed ultrasound. If the mammogram is suspicious or highly suggestive of malignancy, or in cases where the mammogram does not show an abnormality, the next recommended step is breast ultrasonography. Any suspicious findings on ultrasound or mammogram should be followed by an image guided biopsy. Ultrasonography also may be appropriate if the mammogram findings are benign or probably benign.
For an adult woman younger than age 30 who presents with a palpable breast mass, breast ultrasonography is the appropriate initial imaging study. If the ultrasound is suspicious or highly suggestive of malignancy, then performing diagnostic mammography with or without digital tomosynthesis or ultrasound-guided core needle biopsy of the mass are both considered appropriate. However, no further imaging is recommended if the ultrasound is benign, probably benign, or negative. Breast ultrasonography or mammography is appropriate as the initial imaging test for adult women aged 30 to 39 years who present with a palpable breast mass.3,4
Approximately 50% of women after age 30 may develop fibrocystic breast disease, and 20% of them can present with pain or lump due to a macrocysts. Simple cysts must be distinguished from complex cysts with the help of ultrasound as the latter are associated with 23% to 31% increased risk of malignancy.
In this 45-year-old patient, the initial mammogram demonstrated a circumscribed mass underneath the area of palpable concern (FIGURE 1a, 1b). Targeted breast ultrasonography was performed for further assessment, which depicted the mass as a benign simple cyst (FIGURE 1c).
On ultrasound, a simple cyst is an anechoic, well-circumscribed mass with a thin capsule and with increased through transmission. Patients with small and asymptomatic simple cysts do not need imaging follow-up and can return for routine screening mammograms.
A breast surgeon, radiologist, or gynecologist can perform percutaneous aspiration if a cyst is large and symptomatic. A cyst with low-level internal echoes, fluid-fluid, or fluid-debris levels is considered a complicated cyst. Differential diagnosis also includes hematoma, fat necrosis, abscess, and galactocele, depending on the clinical presentation. Fine-needle aspiration or short-interval follow-up5,6 is appropriate for complicated cysts, while incision and drainage is indicated in patients with infected cysts and abscesses. A cyst with a solid component is considered a cystic, solid mass, and core needle biopsy is recommended. The differential diagnosis for cysts with solid components includes intracystic papilloma, papillary carcinoma, ductal carcinoma in situ, and necrotic cancers.5,6
Continue to: CASE 2 Painless breast mass in a young woman...
CASE 2 Painless breast mass in a young woman
A 22-year-old woman presents with a 2-month history of breast lump, which is not associated with pain or nipple discharge. On examination, there is a 2 x 2–cm mass in the right breast at 12 o’clock, 2 cm from the nipple, which is mobile, smooth, and nontender on palpation.
Fibroadenoma
In this 22-year-old, the initial imaging of choice is breast ultrasonography. Breast ultrasonography can differentiate a cystic mass from a solid mass, and it does not involve radiation. Right breast targeted ultrasound showed a circumscribed oval homogeneous hypoechoic mass that is wider than tall (FIGURE 2). The patient desired surgical removal, and a pre-lumpectomy core needle biopsy revealed a fibroadenoma.
Fibroadenoma is the most common benign tumor of the breast. It is most often encountered in premenopausal women. Patients present with a painless breast lump, which is smooth and mobile on palpation. Fibroadenoma can be followed expectantly with repeat ultrasound (to assess over time for growth) if it is small and asymptomatic. No further action is needed if it remains stable. If a patient desires surgical excision, a core needle biopsy is usually performed before lumpectomy.
Excisional biopsy or removal of the mass is recommended if the mass is greater than 3 or 4 cm, is symptomatic, or if there is an increase in size that raises clinical concern for phyllodes tumor. Imaging features that are concerning for phyllodes tumors are size greater than 3 cm, indistinct or microlobulated margins, and heterogeneous echo pattern.7,8 In cases in which the imaging features are concerning for phyllodes tumor and a core needle biopsy is not definitive, wide surgical excision is recommended for definitive diagnosis.8
CASE 3 Patient develops breast mass post-surgery
A 45-year-old woman presents with a tender left breast mass that she noticed 2 months after breast reduction surgery. It has been increasing in size since. On clinical examination, a 4 x 4–cm mass is found at the surgical scar site, which is indurated on palpation and tender.
Fat necrosis
In this 45-year-old, the initial test of choice is diagnostic mammography, which showed a somewhat circumscribed area with fat under the palpable marker (FIGURE 3a). Breast ultrasonography was performed for further evaluation, which was inconclusive as the ultrasound showed ill-defined areas of mixed echogenicity (FIGURE 3b). Breast magnetic resonance imaging (MRI) clearly demonstrated fat necrosis in the area of the palpable lump (FIGURE 3c).
Fat necrosis of the breast is an inflammatory process that is seen after breast trauma or surgery. It can present as an incidental mammogram finding or a palpable mass. The patient may give a history of trauma, breast reduction surgery, or breast cancer surgery followed by radiation treatment. On clinical examination, fat necrosis occasionally can present as a firm mass with skin retraction or swelling concerning for cancer. Imaging features are variable depending on the stage of fat necrosis and inflammation.9-11
A mammogram may demonstrate a circumscribed fat-containing mass, an ill-defined mass, asymmetry or calcified oil cyst, and dystrophic calcifications. On ultrasound, fat necrosis can appear as anechoic or hypoechoic or as a complicated cyst or a mixed cystic, solid mass. MRI demonstrates a circumscribed or irregular fat-containing mass, with or without enhancement, and architectural distortion.
When the imaging features are clearly benign—for example, a circumscribed fat-containing mass on mammogram or on ultrasound or, on MRI, marked hypointensity of fat in the center of a circumscribed mass when compared with surrounding fat (keyhole sign)—no further follow-up is needed. When the imaging features are indeterminate, however, a short-interval follow-up can be considered. In cases with irregular fat-containing mass with enhancement, core needle biopsy is indicated to exclude cancer. If the workup remains inconclusive and the level of clinical suspicion is high, surgical excision can be performed for a definitive diagnosis.12
Continue to: Investigating breast pain: Imaging workup and management...
Investigating breast pain: Imaging workup and management
Breast pain, or mastalgia, is the most common concern of women presenting to a breast clinic and accounts for approximately half of such encounters.13 Causes of breast pain include hormonal changes, fibrocystic changes, musculoskeletal causes (such as costochondritis), lack of support, infection, and injury. While mastalgia often causes patient concern, the risk of malignancy in a woman presenting with breast pain alone is low. Still, it is essential to rule out other findings suspicious for cancer (mass, skin changes, or nipple discharge) with a thorough history and breast examination.
In this section, we review clinical presentation, imaging workup, and management for breast pain.
CASE 4 Woman with noncyclic breast pain
A 26-year-old woman presents to the clinic with mastalgia. The pain is noncyclic and primarily located in the upper outer quadrant of her left breast. There is no history of breast cancer in her family. She has no suspicious findings on the breast examination.
Mastalgia
The test of choice for this 26-year-old with focal left breast pain is targeted breast ultrasound. The patient’s ultrasound image showed no suspicious findings or solid or cystic mass (FIGURE 4).
Two important characteristics of breast pain are whether it is noncyclical and whether it is focal. According to the American College of Radiology, no breast imaging is recommended for clinically insignificant cyclical, nonfocal (greater than 1 quadrant)/diffuse pain, as this type of mastalgia is not associated with malignancy.14
For patients age 40 or older, if they are not up to date with their annual screening mammogram, then a mammogram should be performed. An imaging workup is warranted for clinically significant mastalgia that is noncyclical and focal. Even then, no malignancy is identified in most patients with clinically significant mastalgia; in patients with breast pain as their only symptom, the prevalence of breast cancer is 0% to 3.0%.15-19
The initial imaging modality differs by patient age: younger than 30 years, ultrasonography; between 30 and 40 years, mammography or ultrasonography; and older than 40 years, mammography first followed by ultrasonography.14
Treatment of breast pain is primarily symptomatic, and evidence for specific treatments is generally lacking. Cyclical breast pain resolves spontaneously in 20% to 30% of women, while noncyclical pain responds poorly to treatment but resolves spontaneously in half of women.20 Reassurance is important and wearing a supportive bra often can alleviate breast pain. In addition, reducing caffeine intake can be helpful.
As a first-line treatment, both topical (diclofenac) and oral nonsteroidal anti-inflammatory drugs effectively can relieve breast pain. Supplements and herbal remedies (for example, evening primrose oil, vitamin E, flaxseed) have varying effectiveness and are of questionable benefit as few have trials to support their effectiveness.4 Danazol and tamoxifen have been shown to have some benefits but they also have adverse effects.20 Surgery does not play a role in the treatment of mastalgia.
CASE 5 Breastfeeding woman with breast pain
A 27-year-old postpartum woman presents with concerns for redness and pain in the upper inner left breast. She has been breastfeeding for the past few months. Breast examination demonstrates a 5-cm area of erythema and warmth but no fluctuance or masses.
Lactational mastitis
Targeted ultrasonography is the test of choice for this 27-year-old patient with focal breast pain, and the imaging revealed edema of subcutaneous tissues and ill-defined hypoechoic areas, likely inflamed fat lobules (FIGURE 5). These findings suggest uncomplicated lactational mastitis, which can be treated with antibiotics. Generally, the mastitis will improve within days of starting the antibiotics; if it does not improve, repeat examination and ultrasound should be performed to look for formation of an abscess that may require aspiration.
Continue to: CASE 6 Woman with painful periareolar mass...
CASE 6 Woman with painful periareolar mass
A 42-year-old perimenopausal woman describes having pain near the nipple of her right breast. She is a smoker and has no history of breast cancer in her family. Examination demonstrates a palpable, erythematous, painful, 3-cm periareolar fluctuant mass.
Nonpuerperal periareolar abscess
Appropriate initial imaging for this 42-year-old patient with focal pain is a diagnostic mammogram, which showed skin thickening and a retroareolar mass (FIGURE 6a). Further evaluation with targeted ultrasound showed a thick-walled anechoic collection with echoes compatible with an abscess (FIGURE 6b).
Mammographic findings in a patient with mastitis may be normal or demonstrate skin and trabecular thickening. Ultrasound imaging may show dilated ducts and heterogeneous tissue secondary to inflammation and edema without a discrete fluid collection. In cases with breast abscess, in addition to the mammographic findings described above, a mass, or an asymmetry, may be seen, most commonly in a subareolar location. On ultrasound, a hypoechoic collection with mobile debris, no internal flow on Doppler, and thick hypervascular walls can be seen with abscess, occasionally giving the appearance of a complicated cyst or a mixed cystic, solid mass.
The most important differential for mastitis is inflammatory breast cancer. Most cancers appear solid but can have central necrosis, mimicking a complicated cystic mass on ultrasound. The location for mastitis or abscess is most frequently subareolar. The presence of microcalcifications in a mass indicates the possibility of cancer.
Contrast-enhanced MRI can be helpful to differentiate between infection and cancer, with cancers showing initial early enhancement and washout kinetics compared with infected collections that show no enhancement or peripheral enhancement with a plateau or persistent enhancement curves. When clinical and imaging findings are unchanged after treatment of mastitis and abscesses, a core needle biopsy should be performed.21,22
There are 2 categories of mastitis and breast abscess: lactational and nonpuerperal (all mastitis that occurs outside the lactational period). The World Health Organization definition of puerperal mastitis includes pain, local redness, warmth and swelling of the breast (usually unilateral), fever, and malaise.4 Concerning etiology, epithelial lesions in the nipple area caused by breastfeeding can allow pathogens to enter and cause infection. The most common microorganism is Staphylococcus aureus.4 Continued emptying of the breast is important, combined with early antibiotic therapy (dicloxacillin is often the first line; if the patient is penicillin allergic, use a macrolide such as clindamycin). If no improvement is seen in 48 to 72 hours, imaging should be performed.
In most cases, continuation of breastfeeding is possible. If mastitis has evolved into an abscess in a lactating woman, it can be aspirated under ultrasound guidance. Incision and drainage should be avoided unless the abscess persists after multiple aspiration attempts, it is large, or if the overlying skin is thin or otherwise appears nonviable.
Nonpuerperal mastitis includes peripheral, periductal, and idiopathic granulomatous mastitis (IGM). Peripheral mastitis behaves like infections/abscesses in other soft tissues, responds well to treatment (antibiotics and percutaneous drainage), and is less likely to recur than periductal mastitis and IGM.21,23
Periductal mastitis and abscess, also known as Zuska disease, has a pathogenesis distinct from other forms of mastitis. Squamous metaplasia of the usual cuboidal epithelium of the breast ducts leads to keratin plugging that can cause infection.23 Risk factors include obesity, smoking, and macromastia. The typical presentation of Zuska disease is a woman with a history of chronic smoking and/or a congenital cleft in the central nipple.23 Periareolar signs of inflammation (redness, swelling, warmth) may be accompanied by an abscess. These can recur and lead to chronic fistula formation, especially if there is a history of intervention (such as aspiration, incision, and drainage).
Treatment of Zuska disease includes symptom relief and antibiotics. If S aureus is present, infection with methicillin-resistant S aureus is likely, and treatment with clindamycin or amoxicillin/clavulanic acid is preferred. If abscess is present, aspiration (preferred, often under ultrasound guidance) or incision and drainage (if the skin is compromised) may be required. If disease is recurrent or associated with a chronically draining fistula, surgical intervention may be warranted, in which resolution requires removing the keratin-plugged ducts in and immediately below the central core of the nipple. Given the association between Zuska disease and smoking, cessation should be encouraged, although there is no guarantee that this will resolve the issue.23
Continue to: CASE 7 Patient with breast pain and swelling...
CASE 7 Patient with breast pain and swelling
A 39-year-old woman presents with left breast swelling and pain of 1 month’s duration. On examination, there is a 6-cm area of edema, induration, and erythema.
Granulomatous mastitis
A diagnostic mammogram and ultrasound demonstrated an ill-defined hypoechoic mass (FIGURE 7a). Ultrasound-guided biopsy was performed, which showed granulomatous mastitis, negative for fungus and acid-fast bacilli. The patient was treated with prednisone and gradually improved (FIGURE 7b).
Granulomatous mastitis (GM) is a rare benign inflammatory process, with etiologies that include fungal infections, tuberculosis, Wegener granulomatosis, sarcoidosis, and idiopathic causes. Imaging can be nonspecific and show variable features. Mammograms can appear normal or show asymmetry or mass and skin thickening. Ultrasound can show heterogeneous parenchyma, ill-defined hypoechoic collection, or a mass with margins that can be circumscribed or indistinct or with tubular extensions, with or without overlying skin thickening, fistulas, and reactive lymph nodes.24
In this clinical setting, the differential diagnosis includes infectious mastitis, inflammatory breast cancer, foreign body injection granulomas, and diabetic mastopathy. Treatment involves drainage and fluid culture if there is a collection on imaging. A core biopsy is performed if imaging demonstrates a solid mass or fluid culture is negative and symptoms persist or recur. Oral steroids represent the mainstay of treatment if a core biopsy shows GM. However, immunosuppressants, including methotrexate, and surgery are options if initial treatment is not helpful.25,26
Conclusion
Breast symptoms are common reasons for patient visits to obstetricians and gynecologists. With a good understanding of the various symptomatic breast diseases and conditions, and by having a close collaboration with radiologists and breast surgeons, clinicians can provide excellent care to these patients and thereby improve patient outcomes and satisfaction. ●
The vast majority of symptomatic breast conditions are benign, with the most common symptoms being palpable mass and breast pain. Clinicians, including primary care clinicians and gynecologists, play a crucial role by performing the initial assessment and subsequent therapies and referrals and serve as the mediator between the specialists and by being the patient’s spokesperson. It is therefore important for clinicians to be aware of the various possible causes of these breast symptoms, to know which imaging tests to order, and also to understand the indications for biopsies and surgical referral.
Common types of breast lumps: Imaging workup and management
Accounting for 8% of women who present with breast symptoms, breast lump is the second most common symptom after breast pain.1 The positive likelihood ratio of finding breast cancer is highest among women with breast lumps compared with any other breast symptoms. Therefore, anxiety is related to this symptom, and a thorough evaluation is recommended.1 Cysts, fibroadenoma, and fat necrosis are 3 common benign causes of breast lumps.2
In this section, we review clinical presentation, imaging workup, and management strategies for common types of breast lumps.
CASE 1 Woman with tender breast lump
A 45-year-old woman presents with a breast lump of 6 months’ duration that is associated with a change in size with the menstrual cycle and pain. Clinical examination reveals a 4 x 4.5–cm mass in the right breast in the retroareolar region, which is smooth with some tenderness on palpation.
Breast cyst
According to the American College of Radiology appropriateness criteria for an adult woman 40 years of age or older who presents with a palpable breast mass, the initial imaging study is diagnostic mammography with or without digital tomosynthesis, usually followed by a directed ultrasound. If the mammogram is suspicious or highly suggestive of malignancy, or in cases where the mammogram does not show an abnormality, the next recommended step is breast ultrasonography. Any suspicious findings on ultrasound or mammogram should be followed by an image guided biopsy. Ultrasonography also may be appropriate if the mammogram findings are benign or probably benign.
For an adult woman younger than age 30 who presents with a palpable breast mass, breast ultrasonography is the appropriate initial imaging study. If the ultrasound is suspicious or highly suggestive of malignancy, then performing diagnostic mammography with or without digital tomosynthesis or ultrasound-guided core needle biopsy of the mass are both considered appropriate. However, no further imaging is recommended if the ultrasound is benign, probably benign, or negative. Breast ultrasonography or mammography is appropriate as the initial imaging test for adult women aged 30 to 39 years who present with a palpable breast mass.3,4
Approximately 50% of women after age 30 may develop fibrocystic breast disease, and 20% of them can present with pain or lump due to a macrocysts. Simple cysts must be distinguished from complex cysts with the help of ultrasound as the latter are associated with 23% to 31% increased risk of malignancy.
In this 45-year-old patient, the initial mammogram demonstrated a circumscribed mass underneath the area of palpable concern (FIGURE 1a, 1b). Targeted breast ultrasonography was performed for further assessment, which depicted the mass as a benign simple cyst (FIGURE 1c).
On ultrasound, a simple cyst is an anechoic, well-circumscribed mass with a thin capsule and with increased through transmission. Patients with small and asymptomatic simple cysts do not need imaging follow-up and can return for routine screening mammograms.
A breast surgeon, radiologist, or gynecologist can perform percutaneous aspiration if a cyst is large and symptomatic. A cyst with low-level internal echoes, fluid-fluid, or fluid-debris levels is considered a complicated cyst. Differential diagnosis also includes hematoma, fat necrosis, abscess, and galactocele, depending on the clinical presentation. Fine-needle aspiration or short-interval follow-up5,6 is appropriate for complicated cysts, while incision and drainage is indicated in patients with infected cysts and abscesses. A cyst with a solid component is considered a cystic, solid mass, and core needle biopsy is recommended. The differential diagnosis for cysts with solid components includes intracystic papilloma, papillary carcinoma, ductal carcinoma in situ, and necrotic cancers.5,6
Continue to: CASE 2 Painless breast mass in a young woman...
CASE 2 Painless breast mass in a young woman
A 22-year-old woman presents with a 2-month history of breast lump, which is not associated with pain or nipple discharge. On examination, there is a 2 x 2–cm mass in the right breast at 12 o’clock, 2 cm from the nipple, which is mobile, smooth, and nontender on palpation.
Fibroadenoma
In this 22-year-old, the initial imaging of choice is breast ultrasonography. Breast ultrasonography can differentiate a cystic mass from a solid mass, and it does not involve radiation. Right breast targeted ultrasound showed a circumscribed oval homogeneous hypoechoic mass that is wider than tall (FIGURE 2). The patient desired surgical removal, and a pre-lumpectomy core needle biopsy revealed a fibroadenoma.
Fibroadenoma is the most common benign tumor of the breast. It is most often encountered in premenopausal women. Patients present with a painless breast lump, which is smooth and mobile on palpation. Fibroadenoma can be followed expectantly with repeat ultrasound (to assess over time for growth) if it is small and asymptomatic. No further action is needed if it remains stable. If a patient desires surgical excision, a core needle biopsy is usually performed before lumpectomy.
Excisional biopsy or removal of the mass is recommended if the mass is greater than 3 or 4 cm, is symptomatic, or if there is an increase in size that raises clinical concern for phyllodes tumor. Imaging features that are concerning for phyllodes tumors are size greater than 3 cm, indistinct or microlobulated margins, and heterogeneous echo pattern.7,8 In cases in which the imaging features are concerning for phyllodes tumor and a core needle biopsy is not definitive, wide surgical excision is recommended for definitive diagnosis.8
CASE 3 Patient develops breast mass post-surgery
A 45-year-old woman presents with a tender left breast mass that she noticed 2 months after breast reduction surgery. It has been increasing in size since. On clinical examination, a 4 x 4–cm mass is found at the surgical scar site, which is indurated on palpation and tender.
Fat necrosis
In this 45-year-old, the initial test of choice is diagnostic mammography, which showed a somewhat circumscribed area with fat under the palpable marker (FIGURE 3a). Breast ultrasonography was performed for further evaluation, which was inconclusive as the ultrasound showed ill-defined areas of mixed echogenicity (FIGURE 3b). Breast magnetic resonance imaging (MRI) clearly demonstrated fat necrosis in the area of the palpable lump (FIGURE 3c).
Fat necrosis of the breast is an inflammatory process that is seen after breast trauma or surgery. It can present as an incidental mammogram finding or a palpable mass. The patient may give a history of trauma, breast reduction surgery, or breast cancer surgery followed by radiation treatment. On clinical examination, fat necrosis occasionally can present as a firm mass with skin retraction or swelling concerning for cancer. Imaging features are variable depending on the stage of fat necrosis and inflammation.9-11
A mammogram may demonstrate a circumscribed fat-containing mass, an ill-defined mass, asymmetry or calcified oil cyst, and dystrophic calcifications. On ultrasound, fat necrosis can appear as anechoic or hypoechoic or as a complicated cyst or a mixed cystic, solid mass. MRI demonstrates a circumscribed or irregular fat-containing mass, with or without enhancement, and architectural distortion.
When the imaging features are clearly benign—for example, a circumscribed fat-containing mass on mammogram or on ultrasound or, on MRI, marked hypointensity of fat in the center of a circumscribed mass when compared with surrounding fat (keyhole sign)—no further follow-up is needed. When the imaging features are indeterminate, however, a short-interval follow-up can be considered. In cases with irregular fat-containing mass with enhancement, core needle biopsy is indicated to exclude cancer. If the workup remains inconclusive and the level of clinical suspicion is high, surgical excision can be performed for a definitive diagnosis.12
Continue to: Investigating breast pain: Imaging workup and management...
Investigating breast pain: Imaging workup and management
Breast pain, or mastalgia, is the most common concern of women presenting to a breast clinic and accounts for approximately half of such encounters.13 Causes of breast pain include hormonal changes, fibrocystic changes, musculoskeletal causes (such as costochondritis), lack of support, infection, and injury. While mastalgia often causes patient concern, the risk of malignancy in a woman presenting with breast pain alone is low. Still, it is essential to rule out other findings suspicious for cancer (mass, skin changes, or nipple discharge) with a thorough history and breast examination.
In this section, we review clinical presentation, imaging workup, and management for breast pain.
CASE 4 Woman with noncyclic breast pain
A 26-year-old woman presents to the clinic with mastalgia. The pain is noncyclic and primarily located in the upper outer quadrant of her left breast. There is no history of breast cancer in her family. She has no suspicious findings on the breast examination.
Mastalgia
The test of choice for this 26-year-old with focal left breast pain is targeted breast ultrasound. The patient’s ultrasound image showed no suspicious findings or solid or cystic mass (FIGURE 4).
Two important characteristics of breast pain are whether it is noncyclical and whether it is focal. According to the American College of Radiology, no breast imaging is recommended for clinically insignificant cyclical, nonfocal (greater than 1 quadrant)/diffuse pain, as this type of mastalgia is not associated with malignancy.14
For patients age 40 or older, if they are not up to date with their annual screening mammogram, then a mammogram should be performed. An imaging workup is warranted for clinically significant mastalgia that is noncyclical and focal. Even then, no malignancy is identified in most patients with clinically significant mastalgia; in patients with breast pain as their only symptom, the prevalence of breast cancer is 0% to 3.0%.15-19
The initial imaging modality differs by patient age: younger than 30 years, ultrasonography; between 30 and 40 years, mammography or ultrasonography; and older than 40 years, mammography first followed by ultrasonography.14
Treatment of breast pain is primarily symptomatic, and evidence for specific treatments is generally lacking. Cyclical breast pain resolves spontaneously in 20% to 30% of women, while noncyclical pain responds poorly to treatment but resolves spontaneously in half of women.20 Reassurance is important and wearing a supportive bra often can alleviate breast pain. In addition, reducing caffeine intake can be helpful.
As a first-line treatment, both topical (diclofenac) and oral nonsteroidal anti-inflammatory drugs effectively can relieve breast pain. Supplements and herbal remedies (for example, evening primrose oil, vitamin E, flaxseed) have varying effectiveness and are of questionable benefit as few have trials to support their effectiveness.4 Danazol and tamoxifen have been shown to have some benefits but they also have adverse effects.20 Surgery does not play a role in the treatment of mastalgia.
CASE 5 Breastfeeding woman with breast pain
A 27-year-old postpartum woman presents with concerns for redness and pain in the upper inner left breast. She has been breastfeeding for the past few months. Breast examination demonstrates a 5-cm area of erythema and warmth but no fluctuance or masses.
Lactational mastitis
Targeted ultrasonography is the test of choice for this 27-year-old patient with focal breast pain, and the imaging revealed edema of subcutaneous tissues and ill-defined hypoechoic areas, likely inflamed fat lobules (FIGURE 5). These findings suggest uncomplicated lactational mastitis, which can be treated with antibiotics. Generally, the mastitis will improve within days of starting the antibiotics; if it does not improve, repeat examination and ultrasound should be performed to look for formation of an abscess that may require aspiration.
Continue to: CASE 6 Woman with painful periareolar mass...
CASE 6 Woman with painful periareolar mass
A 42-year-old perimenopausal woman describes having pain near the nipple of her right breast. She is a smoker and has no history of breast cancer in her family. Examination demonstrates a palpable, erythematous, painful, 3-cm periareolar fluctuant mass.
Nonpuerperal periareolar abscess
Appropriate initial imaging for this 42-year-old patient with focal pain is a diagnostic mammogram, which showed skin thickening and a retroareolar mass (FIGURE 6a). Further evaluation with targeted ultrasound showed a thick-walled anechoic collection with echoes compatible with an abscess (FIGURE 6b).
Mammographic findings in a patient with mastitis may be normal or demonstrate skin and trabecular thickening. Ultrasound imaging may show dilated ducts and heterogeneous tissue secondary to inflammation and edema without a discrete fluid collection. In cases with breast abscess, in addition to the mammographic findings described above, a mass, or an asymmetry, may be seen, most commonly in a subareolar location. On ultrasound, a hypoechoic collection with mobile debris, no internal flow on Doppler, and thick hypervascular walls can be seen with abscess, occasionally giving the appearance of a complicated cyst or a mixed cystic, solid mass.
The most important differential for mastitis is inflammatory breast cancer. Most cancers appear solid but can have central necrosis, mimicking a complicated cystic mass on ultrasound. The location for mastitis or abscess is most frequently subareolar. The presence of microcalcifications in a mass indicates the possibility of cancer.
Contrast-enhanced MRI can be helpful to differentiate between infection and cancer, with cancers showing initial early enhancement and washout kinetics compared with infected collections that show no enhancement or peripheral enhancement with a plateau or persistent enhancement curves. When clinical and imaging findings are unchanged after treatment of mastitis and abscesses, a core needle biopsy should be performed.21,22
There are 2 categories of mastitis and breast abscess: lactational and nonpuerperal (all mastitis that occurs outside the lactational period). The World Health Organization definition of puerperal mastitis includes pain, local redness, warmth and swelling of the breast (usually unilateral), fever, and malaise.4 Concerning etiology, epithelial lesions in the nipple area caused by breastfeeding can allow pathogens to enter and cause infection. The most common microorganism is Staphylococcus aureus.4 Continued emptying of the breast is important, combined with early antibiotic therapy (dicloxacillin is often the first line; if the patient is penicillin allergic, use a macrolide such as clindamycin). If no improvement is seen in 48 to 72 hours, imaging should be performed.
In most cases, continuation of breastfeeding is possible. If mastitis has evolved into an abscess in a lactating woman, it can be aspirated under ultrasound guidance. Incision and drainage should be avoided unless the abscess persists after multiple aspiration attempts, it is large, or if the overlying skin is thin or otherwise appears nonviable.
Nonpuerperal mastitis includes peripheral, periductal, and idiopathic granulomatous mastitis (IGM). Peripheral mastitis behaves like infections/abscesses in other soft tissues, responds well to treatment (antibiotics and percutaneous drainage), and is less likely to recur than periductal mastitis and IGM.21,23
Periductal mastitis and abscess, also known as Zuska disease, has a pathogenesis distinct from other forms of mastitis. Squamous metaplasia of the usual cuboidal epithelium of the breast ducts leads to keratin plugging that can cause infection.23 Risk factors include obesity, smoking, and macromastia. The typical presentation of Zuska disease is a woman with a history of chronic smoking and/or a congenital cleft in the central nipple.23 Periareolar signs of inflammation (redness, swelling, warmth) may be accompanied by an abscess. These can recur and lead to chronic fistula formation, especially if there is a history of intervention (such as aspiration, incision, and drainage).
Treatment of Zuska disease includes symptom relief and antibiotics. If S aureus is present, infection with methicillin-resistant S aureus is likely, and treatment with clindamycin or amoxicillin/clavulanic acid is preferred. If abscess is present, aspiration (preferred, often under ultrasound guidance) or incision and drainage (if the skin is compromised) may be required. If disease is recurrent or associated with a chronically draining fistula, surgical intervention may be warranted, in which resolution requires removing the keratin-plugged ducts in and immediately below the central core of the nipple. Given the association between Zuska disease and smoking, cessation should be encouraged, although there is no guarantee that this will resolve the issue.23
Continue to: CASE 7 Patient with breast pain and swelling...
CASE 7 Patient with breast pain and swelling
A 39-year-old woman presents with left breast swelling and pain of 1 month’s duration. On examination, there is a 6-cm area of edema, induration, and erythema.
Granulomatous mastitis
A diagnostic mammogram and ultrasound demonstrated an ill-defined hypoechoic mass (FIGURE 7a). Ultrasound-guided biopsy was performed, which showed granulomatous mastitis, negative for fungus and acid-fast bacilli. The patient was treated with prednisone and gradually improved (FIGURE 7b).
Granulomatous mastitis (GM) is a rare benign inflammatory process, with etiologies that include fungal infections, tuberculosis, Wegener granulomatosis, sarcoidosis, and idiopathic causes. Imaging can be nonspecific and show variable features. Mammograms can appear normal or show asymmetry or mass and skin thickening. Ultrasound can show heterogeneous parenchyma, ill-defined hypoechoic collection, or a mass with margins that can be circumscribed or indistinct or with tubular extensions, with or without overlying skin thickening, fistulas, and reactive lymph nodes.24
In this clinical setting, the differential diagnosis includes infectious mastitis, inflammatory breast cancer, foreign body injection granulomas, and diabetic mastopathy. Treatment involves drainage and fluid culture if there is a collection on imaging. A core biopsy is performed if imaging demonstrates a solid mass or fluid culture is negative and symptoms persist or recur. Oral steroids represent the mainstay of treatment if a core biopsy shows GM. However, immunosuppressants, including methotrexate, and surgery are options if initial treatment is not helpful.25,26
Conclusion
Breast symptoms are common reasons for patient visits to obstetricians and gynecologists. With a good understanding of the various symptomatic breast diseases and conditions, and by having a close collaboration with radiologists and breast surgeons, clinicians can provide excellent care to these patients and thereby improve patient outcomes and satisfaction. ●
- Eberl MM, Phillips RL Jr, Lamberts H, et al. Characterizing breast symptoms in family practice. Ann Fam Med. 2008;6:528-533.
- Malherbe F, Nel D, Molabe H, et al. Palpable breast lumps: an age-based approach to evaluation and diagnosis. S Afr Fam Pract (2022). 2022;64:e1-e5.
- Expert Panel on Breast Imaging; Klein KA, Kocher M, Lourenco AP, et al. American College of Radiology ACR appropriateness criteria: palpable breast masses. Accessed February 15, 2023. https://acsearch.acr.org/docs/69495/Narrative/
- Stachs A, Stubert J, Reimer T, et al. Benign breast disease in women. Dtsch Arztebl Int. 2019;116:565574.
- Hines N, Slanetz PJ, Eisenberg RL. Cystic masses of the breast. AJR Am J Roentgenol. 2010;194:W122133.
- Berg WA. Reducing unnecessary biopsy and follow-up of benign cystic breast lesions. Radiology. 2020;295:52-53.
- Duman L, Gezer NS, Balcı P, et al. Differentiation between phyllodes tumors and fibroadenomas based on mammographic sonographic and MRI features. Breast Care. 2016;11:123-127.
- Lerwill MF, Lee AHS, Tan PH. Fibroepithelial tumours of the breast—a review. Virchows Arch. 2022;480:45-63.
- Vasei N, Shishegar A, Ghalkhani F, et al. Fat necrosis in the breast: a systematic review of clinical. Lipids Health Dis. 2019;18:139.
- Kerridge WD, Kryvenko ON, Thompson A, et al. Fat necrosis of the breast: a pictorial review of the mammographic, ultrasound, CT, and MRI findings with histopathologic correlation. Radiol Res Pract. 2015;2015:613139.
- Taboada JL, Stephens TW, Krishnamurthy S, et al. The many faces of fat necrosis in the breast. AJR Am J Roentgenol. 2009;192:815-825.
- Tan PH, Lai LM, Carrington EV, et al. Fat necrosis of the breast—a review. Breast. 2006;15:313-318.
- Holbrook AI. Breast pain, a common grievance: guidance to radiologists. AJR Am J Roentgenol. 2020;214:259-264.
- Expert Panel on Breast Imaging; Moy L, Heller SL, Bailey L, et al. ACR appropriateness criteria: palpable breast masses. J Am Coll Radiol. 2017;14:S203-S224.
- Chetlen AL, Kapoor MM, Watts MR. Mastalgia: imaging workup appropriateness. Acad Radiol. 2017;24:345-349.
- Arslan M, Kucukerdem HS, Can H, et al. Retrospective analysis of women with only mastalgia. J Breast Health. 2016;12:151-154.
- Fariselli G, Lepera P, Viganotti G, et al. Localized mastalgia as presenting symptom in breast cancer. Eur J Surg Oncol. 1988;14:213-215.
- Leddy R, Irshad A, Zerwas E, et al. Role of breast ultrasound and mammography in evaluating patients presenting with focal breast pain in the absence of a palpable lump. Breast J. 2013;19:582-589.
- Leung JW, Kornguth PJ, Gotway MB. Utility of targeted sonography in the evaluation of focal breast pain. J Ultrasound Med. 2002;21:521-526.
- Goyal A. Breast pain. BMJ Clin Evid. 2011; 2011:0812.
- Kasales CJ, Han B, Smith Jr JS, et al. Nonpuerperal mastitis and subareolar abscess of the breast. AJR Am J Roentgenol. 2014;202:W133-W139.
- Mahoney MC, Ingram AD. Breast emergencies: types, imaging features, and management. AJR Am J Roentgenol. 2014;202:W390-W399.
- Snider HC. Management of mastitis, abscess, and fistula. Surg Clin North Am. 2022;102:1103-1116.
- Oztekin PS, Durhan G, Kosar PN, et al. Imaging findings in patients with granulomatous mastitis. Iran J Radiol. 2016;13:e33900.
- Pluguez-Turull CW, Nanyes JE, Quintero CJ, et al. Idiopathic granulomatous mastitis: manifestations at multimodality imaging and pitfalls. Radiographics. 2018;38:330-356.
- Hovanessian-Larsen LJ, Peyvandi B, Klipfel N, et al. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193:574-581.
- Eberl MM, Phillips RL Jr, Lamberts H, et al. Characterizing breast symptoms in family practice. Ann Fam Med. 2008;6:528-533.
- Malherbe F, Nel D, Molabe H, et al. Palpable breast lumps: an age-based approach to evaluation and diagnosis. S Afr Fam Pract (2022). 2022;64:e1-e5.
- Expert Panel on Breast Imaging; Klein KA, Kocher M, Lourenco AP, et al. American College of Radiology ACR appropriateness criteria: palpable breast masses. Accessed February 15, 2023. https://acsearch.acr.org/docs/69495/Narrative/
- Stachs A, Stubert J, Reimer T, et al. Benign breast disease in women. Dtsch Arztebl Int. 2019;116:565574.
- Hines N, Slanetz PJ, Eisenberg RL. Cystic masses of the breast. AJR Am J Roentgenol. 2010;194:W122133.
- Berg WA. Reducing unnecessary biopsy and follow-up of benign cystic breast lesions. Radiology. 2020;295:52-53.
- Duman L, Gezer NS, Balcı P, et al. Differentiation between phyllodes tumors and fibroadenomas based on mammographic sonographic and MRI features. Breast Care. 2016;11:123-127.
- Lerwill MF, Lee AHS, Tan PH. Fibroepithelial tumours of the breast—a review. Virchows Arch. 2022;480:45-63.
- Vasei N, Shishegar A, Ghalkhani F, et al. Fat necrosis in the breast: a systematic review of clinical. Lipids Health Dis. 2019;18:139.
- Kerridge WD, Kryvenko ON, Thompson A, et al. Fat necrosis of the breast: a pictorial review of the mammographic, ultrasound, CT, and MRI findings with histopathologic correlation. Radiol Res Pract. 2015;2015:613139.
- Taboada JL, Stephens TW, Krishnamurthy S, et al. The many faces of fat necrosis in the breast. AJR Am J Roentgenol. 2009;192:815-825.
- Tan PH, Lai LM, Carrington EV, et al. Fat necrosis of the breast—a review. Breast. 2006;15:313-318.
- Holbrook AI. Breast pain, a common grievance: guidance to radiologists. AJR Am J Roentgenol. 2020;214:259-264.
- Expert Panel on Breast Imaging; Moy L, Heller SL, Bailey L, et al. ACR appropriateness criteria: palpable breast masses. J Am Coll Radiol. 2017;14:S203-S224.
- Chetlen AL, Kapoor MM, Watts MR. Mastalgia: imaging workup appropriateness. Acad Radiol. 2017;24:345-349.
- Arslan M, Kucukerdem HS, Can H, et al. Retrospective analysis of women with only mastalgia. J Breast Health. 2016;12:151-154.
- Fariselli G, Lepera P, Viganotti G, et al. Localized mastalgia as presenting symptom in breast cancer. Eur J Surg Oncol. 1988;14:213-215.
- Leddy R, Irshad A, Zerwas E, et al. Role of breast ultrasound and mammography in evaluating patients presenting with focal breast pain in the absence of a palpable lump. Breast J. 2013;19:582-589.
- Leung JW, Kornguth PJ, Gotway MB. Utility of targeted sonography in the evaluation of focal breast pain. J Ultrasound Med. 2002;21:521-526.
- Goyal A. Breast pain. BMJ Clin Evid. 2011; 2011:0812.
- Kasales CJ, Han B, Smith Jr JS, et al. Nonpuerperal mastitis and subareolar abscess of the breast. AJR Am J Roentgenol. 2014;202:W133-W139.
- Mahoney MC, Ingram AD. Breast emergencies: types, imaging features, and management. AJR Am J Roentgenol. 2014;202:W390-W399.
- Snider HC. Management of mastitis, abscess, and fistula. Surg Clin North Am. 2022;102:1103-1116.
- Oztekin PS, Durhan G, Kosar PN, et al. Imaging findings in patients with granulomatous mastitis. Iran J Radiol. 2016;13:e33900.
- Pluguez-Turull CW, Nanyes JE, Quintero CJ, et al. Idiopathic granulomatous mastitis: manifestations at multimodality imaging and pitfalls. Radiographics. 2018;38:330-356.
- Hovanessian-Larsen LJ, Peyvandi B, Klipfel N, et al. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193:574-581.
Breast cancer screening advice ‘dangerous’ for black women
The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.
But
The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.
The study was published online in JAMA Network Open.
Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.
Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.
“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”
The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.
Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.
The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.
For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).
If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.
If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.
If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.
Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.
“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.
Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.
“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”
The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.
But
The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.
The study was published online in JAMA Network Open.
Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.
Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.
“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”
The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.
Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.
The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.
For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).
If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.
If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.
If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.
Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.
“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.
Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.
“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”
The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.
But
The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.
The study was published online in JAMA Network Open.
Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.
Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.
“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”
The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.
Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.
The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.
For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).
If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.
If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.
If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.
Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.
“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.
Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.
“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”
The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.