User login
Less Than 50% of Accelerated Approvals Show Clinical Benefit
despite being on the US market for more than 5 years, according to a new study.
Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response.
Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.
The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.
In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.
To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits.
Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.
Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results.
The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff.
However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials.
In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”
There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit.
The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious.
In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial.
“There have been some promising steps,” Dr. Cliff said, but much work needs to be done.
Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.”
But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.
Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.”
Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.”
As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together.
The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures.
A version of this article appeared on Medscape.com.
despite being on the US market for more than 5 years, according to a new study.
Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response.
Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.
The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.
In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.
To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits.
Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.
Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results.
The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff.
However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials.
In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”
There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit.
The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious.
In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial.
“There have been some promising steps,” Dr. Cliff said, but much work needs to be done.
Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.”
But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.
Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.”
Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.”
As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together.
The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures.
A version of this article appeared on Medscape.com.
despite being on the US market for more than 5 years, according to a new study.
Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response.
Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.
The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.
In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.
To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits.
Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.
Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results.
The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff.
However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials.
In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”
There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit.
The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious.
In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial.
“There have been some promising steps,” Dr. Cliff said, but much work needs to be done.
Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.”
But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.
Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.”
Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.”
As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together.
The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures.
A version of this article appeared on Medscape.com.
FDA Expands Enhertu Indication to HER2-Positive Solid Tumors
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
Do Tumor-infiltrating Lymphocytes Predict Better Breast Cancer Outcomes?
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
FROM JAMA
Virtual Reality Brings Relief to Hospitalized Patients With Cancer
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
FROM CANCER
Should Opioids Be Used for Chronic Cancer Pain?
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
FROM CANCER
Older, Breastfeeding Mothers Face Differing Advice About Mammograms
When her obstetrician-gynecologist recommended a mammogram, Emily Legg didn’t hesitate to schedule an appointment for the screening.
Her grandmother had been diagnosed with breast cancer and her father died of prostate cancer in his mid-50s. Ms. Legg also has polycystic ovary syndrome (PCOS), which increases the risk of some cancers.
Having just turned 40, Ms. Legg said she was determined to be as proactive as possible with cancer screenings.
Before the mammogram, she arranged for childcare for her 6-month-old daughter and filled out a required questionnaire online that asked about her history and health conditions. When the appointment day arrived, Ms. Legg made the 30-minute drive to the clinic where she was prepped for the procedure and escorted to the mammography room.
But just before the screening started, Ms. Legg happened to mention to the technician that she was breastfeeding. The surprised tech immediately halted the procedure, Ms. Legg said. Because of increased breast density caused by nursing, Ms. Legg was told to wait at least 6 weeks after weaning for a mammogram.
“I didn’t even consider that breastfeeding might prevent me from getting a mammogram,” said Ms. Legg, a writing professor from Hamilton, Ohio. “I had to go home. I was frustrated, mostly because I had driven all that way. I had hyped myself up. I had childcare in line. And now I had to wait until my daughter weaned? At the time, I didn’t know if my daughter was going to breastfeed for 2 years or be done at 6 months.”
Considering her family background, Ms. Legg worried about not receiving the screening. Her sister had recently undergone a mammogram while she was breastfeeding without any problems.
When she did research, Ms. Legg found conflicting information about the subject online so she turned to Reddit, where she started a thread asking if other moms over 40 had experienced similar issues. Dozens of moms responded with questions and concerns on the subject. Some wrote about being denied a mammogram while breastfeeding, while others wrote they received the procedure without question. Guidance from health professionals on the topic appeared to vastly differ.
“That’s why I turned to [social media] because I wasn’t finding anything else,” Ms. Legg said. “There’s just a lack of clear information. As an older mom, there’s less information out there for being postpartum and being over 40.”
Confusion over screenings during breastfeeding comes at the intersection of national guidelines lowering the recommended age for first mammograms, more women having babies later in life, and women getting breast cancer earlier.
Most physician specialty associations agree that mammography is safe for breastfeeding patients and that they need not delay routine screenings. However, the safety of breast imaging during pregnancy and lactation is not well advertised, said Molly Peterson, MD, a radiologist based in St. Frances, Wisconsin, and lead author of a 2023 article about breast imaging during pregnancy and lactation in RadioGraphics, a journal of the Radiological Society of North America.
Conflicting information from nonscientific resources adds to the confusion, Dr. Peterson said. At the same time, health providers along the care spectrum may be uncertain about what imaging is safe and reasonable. Recommendations about mammography and lactation can also vary by institution, screening experts say.
“I’ve talked with pregnant and breastfeeding patients, both younger and older, who were unsure if they could have mammograms,” Dr. Peterson said. “I’ve also fielded questions from technologists, unclear what imaging we can offer these patients. ... Educating health professionals about evidence-based guidelines for screening and diagnostic imaging and reassuring patients about the safety of breast imaging during pregnancy and lactation is thus more important than ever.”
Differing Guidelines, Case-by-Case Considerations
The RadioGraphics paper emphasizes that both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating.
The American College of Radiology (ACR) Appropriateness Criteria also support mammography for certain patients during lactation. The guidelines state there is no contraindication to performing mammography during lactation, but note that challenges in evaluation can arise because of the unique physiological and structural breast changes that can occur.
“Hormones can change breast density and size of the breast, which could limit the clinical examination, mimic pathology, and obscure mammographic findings,” said Stamatia V. Destounis, MD, FACR, chair of the ACR Breast Imaging Commission. “It is important the patient pumps right before the mammogram or brings the baby to breastfeed prior to the imaging examination to offer the best imaging evaluation and reduce breast density as much as possible.”
In those patients who choose to prolong breastfeeding and are of the age to be screened, it is important they undergo yearly clinical breast exams, perform breast self-exams, and discuss breast cancer screening with their healthcare provider, she said. “They should not delay a routine screening mammogram. Most patients have dense breast tissue at this time, and frequently a breast ultrasound may be performed also.”
The American College of Obstetricians and Gynecologists (ACOG) does not have specific guidelines about breastfeeding mothers and mammography recommendations. Breastfeeding patients should discuss with their physicians or midwives the pros and cons of mammography, taking into account personal risk factors and how long they plan to nurse, said Joshua Copel, MD, vice chair of obstetrics, gynecology and reproductive sciences at Yale Medicine, New Haven, Connecticut, and a member of ACOG’s Committee on Obstetric Practice.
“The question for anybody to address with their physician will be, ‘Is my risk of breast cancer high enough that I should take that small risk that they’re going to over- or underread the mammogram because of my nursing status? Or should I wait until I wean the baby and have the mammogram then?’” he said.
Institutional and practice protocols meanwhile, can depend on a patient’s cancer risk.
Guidelines at the University of Wisconsin, for instance, advise that lactating patients 40 or over who are at average risk, wait 6-8 weeks after cessation of breastfeeding, said Alison Gegios, MD, a radiologist and assistant professor in breast imaging at the University of Wisconsin School of Medicine and Public Health. Average risk is defined as less than a 15% lifetime risk of breast cancer, she said.
Dr. Gegios, a coauthor on the RadioGraphics paper, said her institution recommends screening mammography if lactating patients are at intermediate or high risk, and are over 30. In such cases however, screening is generally deferred until 3-6 months after delivery, she noted.
“If patients are high risk, it’s also important to do screening breast MRIs,” Dr. Gegios said. “Studies have shown that screening breast MRIs are effective in breastfeeding patients despite their increased background parenchymal enhancement because breast cancer still stands out on our maximum intensity projections and stands out on the exam from the background.”
How to Clear Up Confusion, Promote Consistency
After her experience at the mammography practice, Ms. Legg went home and immediately sent a message to her ob.gyn. about what happened.
The doctor was similarly surprised and frustrated that Ms. Legg wasn’t able to get the mammogram, she said. To get around the difference in protocols, Ms. Legg’s ob.gyn. referred her to a high-risk clinic in Cincinnati. Ms. Legg’s history qualified her as high risk and she received genetic testing and a breast ultrasound at the clinic, she said.
“The ultrasound showed some shady spots,” Ms. Legg recalled. “They weren’t quite sure what they were. Another ultrasound later, they determined the spots were symmetrical and it ended up not being anything [serious]. Genetic-wise, I did not have any markers for cancer.”
Ms. Legg was relieved and she eventually received a mammogram when she finished breastfeeding, she said. However, she feels the overlap of older, breastfeeding moms and mammography guidelines deserves more attention.
“I would encourage all of us in the ‘geriatric mother’s club,’ to advocate for yourself, do your research, and also turn to your medical professionals and ask questions,” she said. “Make sure you know what they recommend for moms who are older and just had a baby.”
On the provider side, Dr. Destounis said physicians should revisit with patients the most updated guidelines about breastfeeding and mammography at routine appointments.
“Patients and their physicians have to have communication about screening for breast cancer if they are of screening age,” she said.
Dr. Copel advises physicians to run through the risks and benefits of mammograms with older, breastfeeding patients and make a shared decision. “It’s all going to vary with the individual circumstances,” he said. “If someone [has] a BRCA gene and their sister and mother had breast cancer, maybe it’s worth it. If somebody has absolutely no family history and just crossed the threshold for meeting a mammogram [recommendation], then sure, wait.”
Ms. Legg would like to see more professional literature and educational material directed toward the older, breastfeeding population about mammograms.
“At minimum, work together across departments to create an intake form, a questionnaire that is inclusive of everything,” she said. “There should be a question before you even get to the tech that asks, ‘Are you breastfeeding?’ ”
When her obstetrician-gynecologist recommended a mammogram, Emily Legg didn’t hesitate to schedule an appointment for the screening.
Her grandmother had been diagnosed with breast cancer and her father died of prostate cancer in his mid-50s. Ms. Legg also has polycystic ovary syndrome (PCOS), which increases the risk of some cancers.
Having just turned 40, Ms. Legg said she was determined to be as proactive as possible with cancer screenings.
Before the mammogram, she arranged for childcare for her 6-month-old daughter and filled out a required questionnaire online that asked about her history and health conditions. When the appointment day arrived, Ms. Legg made the 30-minute drive to the clinic where she was prepped for the procedure and escorted to the mammography room.
But just before the screening started, Ms. Legg happened to mention to the technician that she was breastfeeding. The surprised tech immediately halted the procedure, Ms. Legg said. Because of increased breast density caused by nursing, Ms. Legg was told to wait at least 6 weeks after weaning for a mammogram.
“I didn’t even consider that breastfeeding might prevent me from getting a mammogram,” said Ms. Legg, a writing professor from Hamilton, Ohio. “I had to go home. I was frustrated, mostly because I had driven all that way. I had hyped myself up. I had childcare in line. And now I had to wait until my daughter weaned? At the time, I didn’t know if my daughter was going to breastfeed for 2 years or be done at 6 months.”
Considering her family background, Ms. Legg worried about not receiving the screening. Her sister had recently undergone a mammogram while she was breastfeeding without any problems.
When she did research, Ms. Legg found conflicting information about the subject online so she turned to Reddit, where she started a thread asking if other moms over 40 had experienced similar issues. Dozens of moms responded with questions and concerns on the subject. Some wrote about being denied a mammogram while breastfeeding, while others wrote they received the procedure without question. Guidance from health professionals on the topic appeared to vastly differ.
“That’s why I turned to [social media] because I wasn’t finding anything else,” Ms. Legg said. “There’s just a lack of clear information. As an older mom, there’s less information out there for being postpartum and being over 40.”
Confusion over screenings during breastfeeding comes at the intersection of national guidelines lowering the recommended age for first mammograms, more women having babies later in life, and women getting breast cancer earlier.
Most physician specialty associations agree that mammography is safe for breastfeeding patients and that they need not delay routine screenings. However, the safety of breast imaging during pregnancy and lactation is not well advertised, said Molly Peterson, MD, a radiologist based in St. Frances, Wisconsin, and lead author of a 2023 article about breast imaging during pregnancy and lactation in RadioGraphics, a journal of the Radiological Society of North America.
Conflicting information from nonscientific resources adds to the confusion, Dr. Peterson said. At the same time, health providers along the care spectrum may be uncertain about what imaging is safe and reasonable. Recommendations about mammography and lactation can also vary by institution, screening experts say.
“I’ve talked with pregnant and breastfeeding patients, both younger and older, who were unsure if they could have mammograms,” Dr. Peterson said. “I’ve also fielded questions from technologists, unclear what imaging we can offer these patients. ... Educating health professionals about evidence-based guidelines for screening and diagnostic imaging and reassuring patients about the safety of breast imaging during pregnancy and lactation is thus more important than ever.”
Differing Guidelines, Case-by-Case Considerations
The RadioGraphics paper emphasizes that both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating.
The American College of Radiology (ACR) Appropriateness Criteria also support mammography for certain patients during lactation. The guidelines state there is no contraindication to performing mammography during lactation, but note that challenges in evaluation can arise because of the unique physiological and structural breast changes that can occur.
“Hormones can change breast density and size of the breast, which could limit the clinical examination, mimic pathology, and obscure mammographic findings,” said Stamatia V. Destounis, MD, FACR, chair of the ACR Breast Imaging Commission. “It is important the patient pumps right before the mammogram or brings the baby to breastfeed prior to the imaging examination to offer the best imaging evaluation and reduce breast density as much as possible.”
In those patients who choose to prolong breastfeeding and are of the age to be screened, it is important they undergo yearly clinical breast exams, perform breast self-exams, and discuss breast cancer screening with their healthcare provider, she said. “They should not delay a routine screening mammogram. Most patients have dense breast tissue at this time, and frequently a breast ultrasound may be performed also.”
The American College of Obstetricians and Gynecologists (ACOG) does not have specific guidelines about breastfeeding mothers and mammography recommendations. Breastfeeding patients should discuss with their physicians or midwives the pros and cons of mammography, taking into account personal risk factors and how long they plan to nurse, said Joshua Copel, MD, vice chair of obstetrics, gynecology and reproductive sciences at Yale Medicine, New Haven, Connecticut, and a member of ACOG’s Committee on Obstetric Practice.
“The question for anybody to address with their physician will be, ‘Is my risk of breast cancer high enough that I should take that small risk that they’re going to over- or underread the mammogram because of my nursing status? Or should I wait until I wean the baby and have the mammogram then?’” he said.
Institutional and practice protocols meanwhile, can depend on a patient’s cancer risk.
Guidelines at the University of Wisconsin, for instance, advise that lactating patients 40 or over who are at average risk, wait 6-8 weeks after cessation of breastfeeding, said Alison Gegios, MD, a radiologist and assistant professor in breast imaging at the University of Wisconsin School of Medicine and Public Health. Average risk is defined as less than a 15% lifetime risk of breast cancer, she said.
Dr. Gegios, a coauthor on the RadioGraphics paper, said her institution recommends screening mammography if lactating patients are at intermediate or high risk, and are over 30. In such cases however, screening is generally deferred until 3-6 months after delivery, she noted.
“If patients are high risk, it’s also important to do screening breast MRIs,” Dr. Gegios said. “Studies have shown that screening breast MRIs are effective in breastfeeding patients despite their increased background parenchymal enhancement because breast cancer still stands out on our maximum intensity projections and stands out on the exam from the background.”
How to Clear Up Confusion, Promote Consistency
After her experience at the mammography practice, Ms. Legg went home and immediately sent a message to her ob.gyn. about what happened.
The doctor was similarly surprised and frustrated that Ms. Legg wasn’t able to get the mammogram, she said. To get around the difference in protocols, Ms. Legg’s ob.gyn. referred her to a high-risk clinic in Cincinnati. Ms. Legg’s history qualified her as high risk and she received genetic testing and a breast ultrasound at the clinic, she said.
“The ultrasound showed some shady spots,” Ms. Legg recalled. “They weren’t quite sure what they were. Another ultrasound later, they determined the spots were symmetrical and it ended up not being anything [serious]. Genetic-wise, I did not have any markers for cancer.”
Ms. Legg was relieved and she eventually received a mammogram when she finished breastfeeding, she said. However, she feels the overlap of older, breastfeeding moms and mammography guidelines deserves more attention.
“I would encourage all of us in the ‘geriatric mother’s club,’ to advocate for yourself, do your research, and also turn to your medical professionals and ask questions,” she said. “Make sure you know what they recommend for moms who are older and just had a baby.”
On the provider side, Dr. Destounis said physicians should revisit with patients the most updated guidelines about breastfeeding and mammography at routine appointments.
“Patients and their physicians have to have communication about screening for breast cancer if they are of screening age,” she said.
Dr. Copel advises physicians to run through the risks and benefits of mammograms with older, breastfeeding patients and make a shared decision. “It’s all going to vary with the individual circumstances,” he said. “If someone [has] a BRCA gene and their sister and mother had breast cancer, maybe it’s worth it. If somebody has absolutely no family history and just crossed the threshold for meeting a mammogram [recommendation], then sure, wait.”
Ms. Legg would like to see more professional literature and educational material directed toward the older, breastfeeding population about mammograms.
“At minimum, work together across departments to create an intake form, a questionnaire that is inclusive of everything,” she said. “There should be a question before you even get to the tech that asks, ‘Are you breastfeeding?’ ”
When her obstetrician-gynecologist recommended a mammogram, Emily Legg didn’t hesitate to schedule an appointment for the screening.
Her grandmother had been diagnosed with breast cancer and her father died of prostate cancer in his mid-50s. Ms. Legg also has polycystic ovary syndrome (PCOS), which increases the risk of some cancers.
Having just turned 40, Ms. Legg said she was determined to be as proactive as possible with cancer screenings.
Before the mammogram, she arranged for childcare for her 6-month-old daughter and filled out a required questionnaire online that asked about her history and health conditions. When the appointment day arrived, Ms. Legg made the 30-minute drive to the clinic where she was prepped for the procedure and escorted to the mammography room.
But just before the screening started, Ms. Legg happened to mention to the technician that she was breastfeeding. The surprised tech immediately halted the procedure, Ms. Legg said. Because of increased breast density caused by nursing, Ms. Legg was told to wait at least 6 weeks after weaning for a mammogram.
“I didn’t even consider that breastfeeding might prevent me from getting a mammogram,” said Ms. Legg, a writing professor from Hamilton, Ohio. “I had to go home. I was frustrated, mostly because I had driven all that way. I had hyped myself up. I had childcare in line. And now I had to wait until my daughter weaned? At the time, I didn’t know if my daughter was going to breastfeed for 2 years or be done at 6 months.”
Considering her family background, Ms. Legg worried about not receiving the screening. Her sister had recently undergone a mammogram while she was breastfeeding without any problems.
When she did research, Ms. Legg found conflicting information about the subject online so she turned to Reddit, where she started a thread asking if other moms over 40 had experienced similar issues. Dozens of moms responded with questions and concerns on the subject. Some wrote about being denied a mammogram while breastfeeding, while others wrote they received the procedure without question. Guidance from health professionals on the topic appeared to vastly differ.
“That’s why I turned to [social media] because I wasn’t finding anything else,” Ms. Legg said. “There’s just a lack of clear information. As an older mom, there’s less information out there for being postpartum and being over 40.”
Confusion over screenings during breastfeeding comes at the intersection of national guidelines lowering the recommended age for first mammograms, more women having babies later in life, and women getting breast cancer earlier.
Most physician specialty associations agree that mammography is safe for breastfeeding patients and that they need not delay routine screenings. However, the safety of breast imaging during pregnancy and lactation is not well advertised, said Molly Peterson, MD, a radiologist based in St. Frances, Wisconsin, and lead author of a 2023 article about breast imaging during pregnancy and lactation in RadioGraphics, a journal of the Radiological Society of North America.
Conflicting information from nonscientific resources adds to the confusion, Dr. Peterson said. At the same time, health providers along the care spectrum may be uncertain about what imaging is safe and reasonable. Recommendations about mammography and lactation can also vary by institution, screening experts say.
“I’ve talked with pregnant and breastfeeding patients, both younger and older, who were unsure if they could have mammograms,” Dr. Peterson said. “I’ve also fielded questions from technologists, unclear what imaging we can offer these patients. ... Educating health professionals about evidence-based guidelines for screening and diagnostic imaging and reassuring patients about the safety of breast imaging during pregnancy and lactation is thus more important than ever.”
Differing Guidelines, Case-by-Case Considerations
The RadioGraphics paper emphasizes that both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating.
The American College of Radiology (ACR) Appropriateness Criteria also support mammography for certain patients during lactation. The guidelines state there is no contraindication to performing mammography during lactation, but note that challenges in evaluation can arise because of the unique physiological and structural breast changes that can occur.
“Hormones can change breast density and size of the breast, which could limit the clinical examination, mimic pathology, and obscure mammographic findings,” said Stamatia V. Destounis, MD, FACR, chair of the ACR Breast Imaging Commission. “It is important the patient pumps right before the mammogram or brings the baby to breastfeed prior to the imaging examination to offer the best imaging evaluation and reduce breast density as much as possible.”
In those patients who choose to prolong breastfeeding and are of the age to be screened, it is important they undergo yearly clinical breast exams, perform breast self-exams, and discuss breast cancer screening with their healthcare provider, she said. “They should not delay a routine screening mammogram. Most patients have dense breast tissue at this time, and frequently a breast ultrasound may be performed also.”
The American College of Obstetricians and Gynecologists (ACOG) does not have specific guidelines about breastfeeding mothers and mammography recommendations. Breastfeeding patients should discuss with their physicians or midwives the pros and cons of mammography, taking into account personal risk factors and how long they plan to nurse, said Joshua Copel, MD, vice chair of obstetrics, gynecology and reproductive sciences at Yale Medicine, New Haven, Connecticut, and a member of ACOG’s Committee on Obstetric Practice.
“The question for anybody to address with their physician will be, ‘Is my risk of breast cancer high enough that I should take that small risk that they’re going to over- or underread the mammogram because of my nursing status? Or should I wait until I wean the baby and have the mammogram then?’” he said.
Institutional and practice protocols meanwhile, can depend on a patient’s cancer risk.
Guidelines at the University of Wisconsin, for instance, advise that lactating patients 40 or over who are at average risk, wait 6-8 weeks after cessation of breastfeeding, said Alison Gegios, MD, a radiologist and assistant professor in breast imaging at the University of Wisconsin School of Medicine and Public Health. Average risk is defined as less than a 15% lifetime risk of breast cancer, she said.
Dr. Gegios, a coauthor on the RadioGraphics paper, said her institution recommends screening mammography if lactating patients are at intermediate or high risk, and are over 30. In such cases however, screening is generally deferred until 3-6 months after delivery, she noted.
“If patients are high risk, it’s also important to do screening breast MRIs,” Dr. Gegios said. “Studies have shown that screening breast MRIs are effective in breastfeeding patients despite their increased background parenchymal enhancement because breast cancer still stands out on our maximum intensity projections and stands out on the exam from the background.”
How to Clear Up Confusion, Promote Consistency
After her experience at the mammography practice, Ms. Legg went home and immediately sent a message to her ob.gyn. about what happened.
The doctor was similarly surprised and frustrated that Ms. Legg wasn’t able to get the mammogram, she said. To get around the difference in protocols, Ms. Legg’s ob.gyn. referred her to a high-risk clinic in Cincinnati. Ms. Legg’s history qualified her as high risk and she received genetic testing and a breast ultrasound at the clinic, she said.
“The ultrasound showed some shady spots,” Ms. Legg recalled. “They weren’t quite sure what they were. Another ultrasound later, they determined the spots were symmetrical and it ended up not being anything [serious]. Genetic-wise, I did not have any markers for cancer.”
Ms. Legg was relieved and she eventually received a mammogram when she finished breastfeeding, she said. However, she feels the overlap of older, breastfeeding moms and mammography guidelines deserves more attention.
“I would encourage all of us in the ‘geriatric mother’s club,’ to advocate for yourself, do your research, and also turn to your medical professionals and ask questions,” she said. “Make sure you know what they recommend for moms who are older and just had a baby.”
On the provider side, Dr. Destounis said physicians should revisit with patients the most updated guidelines about breastfeeding and mammography at routine appointments.
“Patients and their physicians have to have communication about screening for breast cancer if they are of screening age,” she said.
Dr. Copel advises physicians to run through the risks and benefits of mammograms with older, breastfeeding patients and make a shared decision. “It’s all going to vary with the individual circumstances,” he said. “If someone [has] a BRCA gene and their sister and mother had breast cancer, maybe it’s worth it. If somebody has absolutely no family history and just crossed the threshold for meeting a mammogram [recommendation], then sure, wait.”
Ms. Legg would like to see more professional literature and educational material directed toward the older, breastfeeding population about mammograms.
“At minimum, work together across departments to create an intake form, a questionnaire that is inclusive of everything,” she said. “There should be a question before you even get to the tech that asks, ‘Are you breastfeeding?’ ”
Polygenic Risk Scores Improve Breast Cancer Screening
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
A Banned Chemical That Is Still Causing Cancer
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Active Surveillance for Cancer Doesn’t Increase Malpractice Risk
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
Women’s Cancers: Clinicians Research, Advise on Sexual Dysfunction
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
FROM SGO 2024