Metastatic Breast Cancer

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

A version of this article first appeared on Medscape.com.

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

A version of this article first appeared on Medscape.com.

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

A version of this article first appeared on Medscape.com.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

A new pilot study has shown that refractory, hormone-positive metastatic breast cancer can respond to treatment with autologous tumor-infiltrating lymphocytes (TILs) that recognize specific tumor antigens. Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).

The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.

Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.

There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.

In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.

Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.

Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.

Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.

The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.

The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.

A new pilot study has shown that refractory, hormone-positive metastatic breast cancer can respond to treatment with autologous tumor-infiltrating lymphocytes (TILs) that recognize specific tumor antigens. Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).

The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.

Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.

There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.

In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.

Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.

Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.

Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.

The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.

The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.

A new pilot study has shown that refractory, hormone-positive metastatic breast cancer can respond to treatment with autologous tumor-infiltrating lymphocytes (TILs) that recognize specific tumor antigens. Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).

The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.

Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.

There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.

In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.

Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.

Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.

Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.

The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.

The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.

A drop-off in cancer screening during the first year of the COVID-19 pandemic has led to a marked increase in people presenting with advanced breast and colon cancer at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.

“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.

As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.

The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”

The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.

While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.

The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.

It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.

After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).

Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.

One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.

No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.

A version of this article first appeared on Medscape.com.

A drop-off in cancer screening during the first year of the COVID-19 pandemic has led to a marked increase in people presenting with advanced breast and colon cancer at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.

“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.

As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.

The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”

The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.

While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.

The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.

It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.

After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).

Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.

One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.

No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.

A version of this article first appeared on Medscape.com.

A drop-off in cancer screening during the first year of the COVID-19 pandemic has led to a marked increase in people presenting with advanced breast and colon cancer at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.

“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.

As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.

The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”

The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.

While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.

The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.

It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.

After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).

Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.

One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.

No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.

A version of this article first appeared on Medscape.com.

A study comparing the cost of hypofractionated radiotherapy for early-stage breast cancer with the more expensive multidose conventional form, finds that physicians are increasingly opting for hypofractionated radiotherapy despite lower reimbursements rates for the procedure.

Hypofractionated radiotherapy is administered in fewer fractions requiring fewer hospital visits, which, in turn, should lead to less expensive procedures. According to previously reported randomized controlled trials of patients with early breast cancer, both procedures are equally efficacious. In 2011, the American Society of Radiation Oncology published guidelines recommending hypofractionated whole-breast irradiation for patients who have not undergone chemotherapy and who are at least 50 years old with a small primary tumor (T1-2).

In the new study, Loren Saulsberry, PhD, of the department of public health at the University of Chicago, and colleagues Chuanhong Liao and Dezheng Huo, hypothesized that a fee-for-service incentive structure in which doctors are paid by volume and quantity of services, would drive up use of conventional therapy among patients with commercial insurance. And, they hypothesized that, when presented with a smaller cost difference between the two procedures, physicians would recommend hypofractionated radiotherapy over the conventional form, but neither theory was proven true.

This was a retrospective study of private employer–sponsored health insurance claims processed between 2008 and 2017 for women with early-stage breast cancer who were treated with lumpectomy and whole-breast irradiation.

The study included 15,869 women who received hypofractionated radiotherapy and 59,328 who received the conventional form. Women who underwent hypofractionated radiotherapy received 15-24 fractions over 21-31 days. Those who received conventional radiotherapy received 25-40 fractions over 39-120 days. The primary outcomes and measures were the use of hypofractionated or conventional radiotherapy, costs incurred by insurers and out-of-pocket patient expenses.

Dr. Saulsberry and colleagues found the use of hypofractionated radiotherapy increased during this period. They found no association between the likelihood of receiving hypofractionated radiotherapy and insurance plan characteristics. At $23,286, conventional radiotherapy was $6,253 more expensive than hypofractionated radiotherapy which averaged $17,763.

After out-of-pocket expenses were paid (average of $502 for conventional and $363 for hypofractionated radiotherapy), insurers paid an average of $6,375 more for conventional therapy after adjustments.

“Hypofractionated radiotherapy represents significant savings to both the health care system and to individual patients. It may soon become the dominant form of radiation treatment in the U.S. if current trends continue,” Dr. Saulsberry said in an interview after she presented the study (Abstract P3-19-07) at the San Antonio Breast Cancer Symposium.

According to the National Cancer Institute, the cost of cancer care grew from $190.2 billion in 2015 to $208.9 billion in 2020.

Dr. Saulsberry declared no conflicts of interest.

A study comparing the cost of hypofractionated radiotherapy for early-stage breast cancer with the more expensive multidose conventional form, finds that physicians are increasingly opting for hypofractionated radiotherapy despite lower reimbursements rates for the procedure.

Hypofractionated radiotherapy is administered in fewer fractions requiring fewer hospital visits, which, in turn, should lead to less expensive procedures. According to previously reported randomized controlled trials of patients with early breast cancer, both procedures are equally efficacious. In 2011, the American Society of Radiation Oncology published guidelines recommending hypofractionated whole-breast irradiation for patients who have not undergone chemotherapy and who are at least 50 years old with a small primary tumor (T1-2).

In the new study, Loren Saulsberry, PhD, of the department of public health at the University of Chicago, and colleagues Chuanhong Liao and Dezheng Huo, hypothesized that a fee-for-service incentive structure in which doctors are paid by volume and quantity of services, would drive up use of conventional therapy among patients with commercial insurance. And, they hypothesized that, when presented with a smaller cost difference between the two procedures, physicians would recommend hypofractionated radiotherapy over the conventional form, but neither theory was proven true.

This was a retrospective study of private employer–sponsored health insurance claims processed between 2008 and 2017 for women with early-stage breast cancer who were treated with lumpectomy and whole-breast irradiation.

The study included 15,869 women who received hypofractionated radiotherapy and 59,328 who received the conventional form. Women who underwent hypofractionated radiotherapy received 15-24 fractions over 21-31 days. Those who received conventional radiotherapy received 25-40 fractions over 39-120 days. The primary outcomes and measures were the use of hypofractionated or conventional radiotherapy, costs incurred by insurers and out-of-pocket patient expenses.

Dr. Saulsberry and colleagues found the use of hypofractionated radiotherapy increased during this period. They found no association between the likelihood of receiving hypofractionated radiotherapy and insurance plan characteristics. At $23,286, conventional radiotherapy was $6,253 more expensive than hypofractionated radiotherapy which averaged $17,763.

After out-of-pocket expenses were paid (average of $502 for conventional and $363 for hypofractionated radiotherapy), insurers paid an average of $6,375 more for conventional therapy after adjustments.

“Hypofractionated radiotherapy represents significant savings to both the health care system and to individual patients. It may soon become the dominant form of radiation treatment in the U.S. if current trends continue,” Dr. Saulsberry said in an interview after she presented the study (Abstract P3-19-07) at the San Antonio Breast Cancer Symposium.

According to the National Cancer Institute, the cost of cancer care grew from $190.2 billion in 2015 to $208.9 billion in 2020.

Dr. Saulsberry declared no conflicts of interest.

A study comparing the cost of hypofractionated radiotherapy for early-stage breast cancer with the more expensive multidose conventional form, finds that physicians are increasingly opting for hypofractionated radiotherapy despite lower reimbursements rates for the procedure.

Hypofractionated radiotherapy is administered in fewer fractions requiring fewer hospital visits, which, in turn, should lead to less expensive procedures. According to previously reported randomized controlled trials of patients with early breast cancer, both procedures are equally efficacious. In 2011, the American Society of Radiation Oncology published guidelines recommending hypofractionated whole-breast irradiation for patients who have not undergone chemotherapy and who are at least 50 years old with a small primary tumor (T1-2).

In the new study, Loren Saulsberry, PhD, of the department of public health at the University of Chicago, and colleagues Chuanhong Liao and Dezheng Huo, hypothesized that a fee-for-service incentive structure in which doctors are paid by volume and quantity of services, would drive up use of conventional therapy among patients with commercial insurance. And, they hypothesized that, when presented with a smaller cost difference between the two procedures, physicians would recommend hypofractionated radiotherapy over the conventional form, but neither theory was proven true.

This was a retrospective study of private employer–sponsored health insurance claims processed between 2008 and 2017 for women with early-stage breast cancer who were treated with lumpectomy and whole-breast irradiation.

The study included 15,869 women who received hypofractionated radiotherapy and 59,328 who received the conventional form. Women who underwent hypofractionated radiotherapy received 15-24 fractions over 21-31 days. Those who received conventional radiotherapy received 25-40 fractions over 39-120 days. The primary outcomes and measures were the use of hypofractionated or conventional radiotherapy, costs incurred by insurers and out-of-pocket patient expenses.

Dr. Saulsberry and colleagues found the use of hypofractionated radiotherapy increased during this period. They found no association between the likelihood of receiving hypofractionated radiotherapy and insurance plan characteristics. At $23,286, conventional radiotherapy was $6,253 more expensive than hypofractionated radiotherapy which averaged $17,763.

After out-of-pocket expenses were paid (average of $502 for conventional and $363 for hypofractionated radiotherapy), insurers paid an average of $6,375 more for conventional therapy after adjustments.

“Hypofractionated radiotherapy represents significant savings to both the health care system and to individual patients. It may soon become the dominant form of radiation treatment in the U.S. if current trends continue,” Dr. Saulsberry said in an interview after she presented the study (Abstract P3-19-07) at the San Antonio Breast Cancer Symposium.

According to the National Cancer Institute, the cost of cancer care grew from $190.2 billion in 2015 to $208.9 billion in 2020.

Dr. Saulsberry declared no conflicts of interest.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

A version of this article first appeared on Medscape.com.

Greater access to next-generation sequencing (NGS) testing enabled by the national coverage determination (NCD) issued by Medicare in 2018 has not narrowed racial and ethnic disparities in uptake, according to an analysis of data from patients with advanced non–small cell lung cancer (aNSCLC), metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma. The finding was reported in JAMA Network Open.

Biomarker testing has become an essential tool in cancer care over the last decade. In 2011, for example, less than 1% of patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, and advanced melanoma underwent NGS testing, but by 2019, 40% of patients with these cancers received the testing.

“Next-generation sequencing testing has become increasingly important because it enables identification of multiple biomarkers simultaneously and efficiently while minimizing the number of biopsies required,” wrote the authors, led by William B. Wong, PharmD, of Genentech.

It has been unknown whether for Medicare beneficiaries and the overall population, if the NCD affected health equity issues, the authors wrote. While increased use of appropriate targeted therapies facilitated by NGS testing is associated with improved survival rates in patients with advanced or metastatic cancer, variability in health care coverage policies has posed a significant barrier to obtaining NGS testing for cancer patients, specifically through policy coverage limitations. It has remained unclear if the NCD has influenced NGS testing coverage in insurance types (for example, Medicaid) encompassing a larger population of minority racial and ethnic groups often experiencing poorer care and outcomes.

The retrospective cohort analysis compared EHR data from 280 U.S. cancer clinics in the (800 sites of care) pre- versus post-NCD period for patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma (January 2011–March 2020). Nearly 70% of all patients in the study were Medicare recipients who needed NCD approval to cover the cost of testing.

Among 92,687 patients (mean age, 66.6 years; 55.7% women), compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio, 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03), compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not significantly different statistically compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). Also, the NCD was not associated with racial and ethnic groups within Medicare beneficiaries alone or across all insurance types.

Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases were similar, however, among Asian individuals and other races and ethnicities.

The authors observed that the post-NCD trend of increasing NGS testing seen in Medicare beneficiaries was similarly observed in those with commercial insurance. Testing rate differences, however, widened or were maintained after versus before the NCD in PAP (personal assistance program) and Medicaid beneficiaries relative to Medicare beneficiaries, suggesting that access to NGS testing did not improve equally across insurance types. Since Medicare coverage is determined at the state level, the authors urged research examining individual state coverage policies to further elucidate factors slowing uptake among Medicaid beneficiaries. “Additional efforts beyond coverage policies,” the authors concluded, “are needed to ensure equitable access to the benefits of precision medicine.”

The study was supported by Genentech.

Greater access to next-generation sequencing (NGS) testing enabled by the national coverage determination (NCD) issued by Medicare in 2018 has not narrowed racial and ethnic disparities in uptake, according to an analysis of data from patients with advanced non–small cell lung cancer (aNSCLC), metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma. The finding was reported in JAMA Network Open.

Biomarker testing has become an essential tool in cancer care over the last decade. In 2011, for example, less than 1% of patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, and advanced melanoma underwent NGS testing, but by 2019, 40% of patients with these cancers received the testing.

“Next-generation sequencing testing has become increasingly important because it enables identification of multiple biomarkers simultaneously and efficiently while minimizing the number of biopsies required,” wrote the authors, led by William B. Wong, PharmD, of Genentech.

It has been unknown whether for Medicare beneficiaries and the overall population, if the NCD affected health equity issues, the authors wrote. While increased use of appropriate targeted therapies facilitated by NGS testing is associated with improved survival rates in patients with advanced or metastatic cancer, variability in health care coverage policies has posed a significant barrier to obtaining NGS testing for cancer patients, specifically through policy coverage limitations. It has remained unclear if the NCD has influenced NGS testing coverage in insurance types (for example, Medicaid) encompassing a larger population of minority racial and ethnic groups often experiencing poorer care and outcomes.

The retrospective cohort analysis compared EHR data from 280 U.S. cancer clinics in the (800 sites of care) pre- versus post-NCD period for patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma (January 2011–March 2020). Nearly 70% of all patients in the study were Medicare recipients who needed NCD approval to cover the cost of testing.

Among 92,687 patients (mean age, 66.6 years; 55.7% women), compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio, 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03), compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not significantly different statistically compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). Also, the NCD was not associated with racial and ethnic groups within Medicare beneficiaries alone or across all insurance types.

Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases were similar, however, among Asian individuals and other races and ethnicities.

The authors observed that the post-NCD trend of increasing NGS testing seen in Medicare beneficiaries was similarly observed in those with commercial insurance. Testing rate differences, however, widened or were maintained after versus before the NCD in PAP (personal assistance program) and Medicaid beneficiaries relative to Medicare beneficiaries, suggesting that access to NGS testing did not improve equally across insurance types. Since Medicare coverage is determined at the state level, the authors urged research examining individual state coverage policies to further elucidate factors slowing uptake among Medicaid beneficiaries. “Additional efforts beyond coverage policies,” the authors concluded, “are needed to ensure equitable access to the benefits of precision medicine.”

The study was supported by Genentech.

Greater access to next-generation sequencing (NGS) testing enabled by the national coverage determination (NCD) issued by Medicare in 2018 has not narrowed racial and ethnic disparities in uptake, according to an analysis of data from patients with advanced non–small cell lung cancer (aNSCLC), metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma. The finding was reported in JAMA Network Open.

Biomarker testing has become an essential tool in cancer care over the last decade. In 2011, for example, less than 1% of patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, and advanced melanoma underwent NGS testing, but by 2019, 40% of patients with these cancers received the testing.

“Next-generation sequencing testing has become increasingly important because it enables identification of multiple biomarkers simultaneously and efficiently while minimizing the number of biopsies required,” wrote the authors, led by William B. Wong, PharmD, of Genentech.

It has been unknown whether for Medicare beneficiaries and the overall population, if the NCD affected health equity issues, the authors wrote. While increased use of appropriate targeted therapies facilitated by NGS testing is associated with improved survival rates in patients with advanced or metastatic cancer, variability in health care coverage policies has posed a significant barrier to obtaining NGS testing for cancer patients, specifically through policy coverage limitations. It has remained unclear if the NCD has influenced NGS testing coverage in insurance types (for example, Medicaid) encompassing a larger population of minority racial and ethnic groups often experiencing poorer care and outcomes.

The retrospective cohort analysis compared EHR data from 280 U.S. cancer clinics in the (800 sites of care) pre- versus post-NCD period for patients with aNSCLC, metastatic colorectal cancer, metastatic breast cancer, or advanced melanoma (January 2011–March 2020). Nearly 70% of all patients in the study were Medicare recipients who needed NCD approval to cover the cost of testing.

Among 92,687 patients (mean age, 66.6 years; 55.7% women), compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio, 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03), compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not significantly different statistically compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). Also, the NCD was not associated with racial and ethnic groups within Medicare beneficiaries alone or across all insurance types.

Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases were similar, however, among Asian individuals and other races and ethnicities.

The authors observed that the post-NCD trend of increasing NGS testing seen in Medicare beneficiaries was similarly observed in those with commercial insurance. Testing rate differences, however, widened or were maintained after versus before the NCD in PAP (personal assistance program) and Medicaid beneficiaries relative to Medicare beneficiaries, suggesting that access to NGS testing did not improve equally across insurance types. Since Medicare coverage is determined at the state level, the authors urged research examining individual state coverage policies to further elucidate factors slowing uptake among Medicaid beneficiaries. “Additional efforts beyond coverage policies,” the authors concluded, “are needed to ensure equitable access to the benefits of precision medicine.”

The study was supported by Genentech.

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

A version of this article first appeared on Medscape.com.

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

A version of this article first appeared on Medscape.com.

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

A version of this article first appeared on Medscape.com.