Metastatic Breast Cancer

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

[email protected]

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

[email protected]

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

[email protected]

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

The cutoff for programmed death–ligand 1 (PD-L1) combined positive score (CPS) of at least 10 for using pembrolizumab (Keytruda) to treat metastatic triple-negative breast cancer (mTNBC) is able to identify patients who are expected to derive most benefit, shows an analysis of KEYNOTE-355 recently presented at the San Antonio Breast Cancer Symposium.

Patients enrolled in KEYNOTE-355 – which is a phase 3, placebo-controlled trial of 847 patients – were stratified by CPS scores of at least 1 and at least 10, with the latter group in which adding pembrolizumab to chemotherapy was shown to significantly improve both overall survival and progression-free survival.

As it was unclear whether taking a more fine-grained approach would reveal specific CPS scores at which pembrolizumab would be beneficial, Javier Cortes, MD, PhD, International Breast Cancer Center, Barcelona, and colleagues divided the patients into four CPS levels: less than 1, 1-9, 10-19, and at least 20.

Patients with a CPS 10-19 and at least 20 given pembrolizumab alongside chemotherapy had an overall survival benefit of 29% and 28%, respectively, while the PFS improvement was 30% and 38%. In the CPS of less than 1 and 1-9 groups, there were no discernible benefits from adding the checkpoint inhibitor.

“Given the similar outcomes in the CPS 10-19 and the CPS ≥20 subgroups, a CPS of 10 or more is a reasonable cutoff to define the population of patients with metastatic TNBC that might have benefit from the addition of pembrolizumab to chemotherapy,” Dr. Cortes said. “In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option, maybe a standard of care for some patients ... with local recurrent unresectable or metastatic TNBC whose tumors express PD-1 CPS ≥10.”

Invited discussant Hope S. Rugo, MD, said the study demonstrates that PD-L1 CPS of at least 10 is “clearly the optimal cutoff for differentiating benefit from pembrolizumab” and confirms the combination with chemotherapy as a “standard of care in this population”.

However, there are a number of outstanding questions in the metastatic setting, she said, including the test used to determine PD-L1 expression.

“Clearly the test that you order should be matched to the planned checkpoint inhibitor, and we look forward to additional data” on the relative overlap of the assays used in both the current study and in KEYNOTE-522.

However, IMpassion130 showed there is “incomplete overlap in terms of the two antibodies and tests that have been used to define PD-L1 positivity in breast cancer,” said Dr. Rugo, professor of medicine in hematology and oncology at the University of California, San Francisco.

“For excellent responders, can chemotherapy and eventually immunotherapy be discontinued, and when is it optimal? How long should we be continuing the combination and how long should we continue the checkpoint inhibitor alone?” she asked.

“Certainly in my own clinical practice,” Dr. Rugo explained, “in those excellent responders, it’s difficult to know when to stop the checkpoint inhibitor, but sometimes toxicity tells us the answer to that question. At some point, we need to stop therapy and understand what happens to those patients.”

She said that only 38% of patients in the current study benefited from pembrolizumab. “How can we amplify the immune response in those patients who do not have PD-L1–positive disease to further extend this benefit, and can we extend the efficacy to other subtypes? There are ongoing studies evaluating this question,” Dr. Rugo said.

Dr. Cortes said that KEYNOTE-355 showed the addition of pembrolizumab to chemotherapy led to clinically meaningful improvements in both PFS and overall survival versus chemotherapy alone in the first-line treatment of mTNBC.

However, that benefit was seen only in patients with a PD-L1 CPS of at least 10, while there was no statistically significant improvement in either PFS or overall survival in those with a CPS of at least 1.

He explained that 847 patients with previously untreated locally recurrent or metastatic TNBC, or those who had been treated at least 6 months prior to disease recurrence, were randomized 2:1 to pembrolizumab or placebo plus chemotherapy.

For the current analysis, they substratified patients by PD-L1 CPS into less than 1, which accounted for 24.9% of patients; 1-9, seen in 36.2%-38.4%; 10-19, accounting for 13.9%-14.1%; and at least 20, seen in 22.8%-24.7% of patients.

Dr. Cortes said the overall survival rate among patients with CPS of at least 10 was 70.5% for patients treated with pembrolizumab plus chemotherapy versus 81.6% for those assigned to placebo, at a significant hazard ratio of 0.73 (P = .0093).

Among patients with CPS of at least 1, the overall survival rate was 79.1% with pembrolizumab plus chemotherapy and 83.9% in those given placebo, at a nonsignificant hazard ratio of 0.86. This translated into an HR of 0.89 in the intention-to-treat analysis.

Turning to the novel subgroups, Dr. Cortes showed that the HR for overall survival for pembrolizumab versus placebo was nonsignificant in patients with CPS of at least 1, at 0.97, and in those with CPS 1-9, at 1.09.

However, the HRs were markedly improved in patients with CPD 10-19, at 0.71, and in those with CPS of at least 20, at 0.72, showing that the “relative benefit of adding pembrolizumab to chemotherapy was pretty much the same ... suggesting that CPS ≥10 could be a reasonable cutoff.”

In both of these groups, there was a sustained separation in the overall survival curves starting at around 10 months.

Turning to the PFS results, Dr Cortes said the event-free rate was 65.5% with the addition of pembrolizumab to chemotherapy in patients with PD-L1 CPS of at least 10, while those given placebo had a rate of 78.6%, at an HR of 0.66.

In patients with PD-L1 CPS of at least 1, the HR was 0.75, or 0.82 in the intention-to-treat analysis.

“As with overall survival,” he said, there was a “trend toward improved efficacy with PD-L1 enrichment with the addition of pembrolizumab to chemotherapy, although the PFS benefit in the pembro arm was slightly greater in the CPS ≥20 subgroup, compared to the CPS 10-19 subgroup.”

However, they highlighted that the difference was “small and the confidence intervals clearly overlapped.”

Why does PD-L1 expression play a role in response to pembrolizumab in mTNBC, but not in the early disease setting as seen in KEYNOTE-522?

“This is a question we have raised many, many times and have had many debates on,” Dr. Cortes said. “They are two completely different populations with the early breast cancer setting completely different to that in metastatic disease. Maybe the microenvironment plays a different role there, maybe we have to explore more in detail other biomarkers. I also think that different drugs were used in the neoadjuvant setting. We still have many unanswered questions.”

Dr. Rugo suggested that previous studies have given some clues to these questions with reductions in PD-L1 expression and tumor-infiltrating leukocytes observed between primary and metastatic disease.

The immune differences between primary and metastatic disease lead to immune escape, she said, adding: “This is clearly complicated by mutational complexity under the pressure of treatment.”

The study was funded by Merck Sharp and Dohme. Dr. Cortes and Dr. Rugo reported relationships with numerous pharmaceutical companies.

The benefit of giving pembolizumab (Keytruda, Merck) in the neoadjuvant and adjuvant setting to patients with early triple-negative breast cancer (TNBC) extends across subgroups and clinical situations, suggests the latest analysis from KEYNOTE-522.

The original trial data in more than 1,100 patients with early-stage TNBC indicated that adding pembrolizumab to chemotherapy prior to surgery and giving the drug for a year afterward improves event-free survival (EFS) over placebo by 37%.

Now, the researchers conducted a series of prespecified sensitivity and subgroup analyses, finding remarkably consistent EFS outcomes whether considering the addition of adjuvant chemotherapy, positive surgical margins, or disease characteristics such as nodal status and disease stage.

The analyses showed that the benefit with pembrolizumab over placebo was “robust,” said study presenter Peter Schmid, MD, PhD, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London.

“These results further support pembrolizumab plus platinum-containing neoadjuvant chemotherapy followed by adjuvant pembrolizumab after surgery as a new standard of care treatment regimen for patients with high-risk, early-stage TNBC,” he said.

The research was presented at the San Antonio Breast Cancer Symposium on Dec. 7.

Hope S. Rugo, MD, who was invited to comment on the findings, noted that, while the sensitivity analyses showed the benefit with pembrolizumab was seen across the board, the numbers in each group of interest were “very small, making any impact unlikely.”

She continued that there also remain a number of unanswered questions, chief among them being: “Does everybody need a checkpoint inhibitor? Perhaps studies ... could help us understand which patients might do well with chemotherapy alone.”

Dr. Rugo, who is professor of medicine in the division of hematology and oncology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, , added that “we need to understand the balance of risk and toxicity” asking whether there are patients whose risk of an immunotoxicity is “so high that we should not give them a checkpoint inhibitor.”

It is not clear what constitutes the optimal chemotherapy backbone. “Does everybody need carboplatin? Does everyone need a year of pembrolizumab, even with a pathologic complete response given the intriguing data from GeparNUEVO and previously the I-SPY trial?” she asked.

“Of course, we don’t know the answers to those questions,” she said, but it is nevertheless possible to draw a roadmap for the treatment of early TNBC, although the choice of adjuvant therapy following surgery is less clear.

Dr. Rugo conducted a Twitter poll to canvas opinion on what to give to patients following surgery, depending on whether or not they have a pathological complete response.

At 73%, most of almost 200 respondents said patients with a pathological complete response should continue pembrolizumab for 1 year, while 72% said that patients without a pathological complete response should receive combination therapy of pembrolizumab and either capecitabine or olaparib, depending on mutational status.

Dr. Schmid began his presentation by noting that KEYNOTE-522 was the first prospective, randomized, phase 3 trial of pembrolizumab in early TNBC in the neoadjuvant and adjuvant setting.

Previously presented results showed that adding neoadjuvant pembrolizumab to chemotherapy was associated with a clinically meaningful increase in pathological complete response, while continuing with adjuvant chemotherapy after surgery led to a clinically meaningful improvement in EFS.

Consequently, the Food and Drug Administration approved pembrolizumab in this setting for patients with high-risk early-stage TNBC.

He reminded the audience that the trial included 1,174 patients randomized 2:1 to pembrolizumab or placebo every 3 weeks alongside eight cycles of chemotherapy, followed by pembrolizumab over placebo alone for up to nine cycles after undergoing definitive surgery.

After a median follow-up of 39.1 months, 15.7% of patients treated with pembrolizumab experienced an event versus 23.9% of those in the placebo group, at a hazard ratio of 0.63 (P = .00031). At 36 months, the EFS rate was 84.5% with pembrolizumab and 76.8% in patients treated with placebo.

Dr. Schmid said that they then performed five prespecified sensitivity analyses, which revealed that the results were “consistent with the primary EFS in all five sensitivity analyses, showing the robustnesses of the event-free survival benefit in the pembrolizumab arm.”

The first analysis, he continued, is of “particular interest as it considered the impact of postsurgery new anticancer therapy. For example, the use of adjuvant capecitabine.”

Censoring 31 patients from the pembrolizumab arm who received the drug and 13 of those given placebo, the team found that the hazard ratio for EFS for pembrolizumab versus placebo was 0.64.

Removing “positive margin at last surgery” as part of the definition of EFS also did not change the results substantially, with the HR for EFS for pembrolizumab versus placebo at 0.65.

Subgroup analysis revealed “consistent EFS results,” Dr. Schmid said, irrespective of whether stratifying the patients by nodal status, overall disease stage, menopausal status, HER2 status, or lactate dehydrogenase levels.

While patients in both treatment arms who had nodal involvement had worse outcomes than those without, those in the pembrolizumab arm “still had improved outcomes, compared with placebo, suggesting that it provides benefit regardless of nodal status.”

“Similarly, the EFS benefit with pembrolizumab was irrespective of disease stage,” Dr. Schmid said. Although the EFS improvement was greater in patients with stage II rather than III disease, at a HR of 0.60 versus 0.68, it highlights “the importance of early intervention.”

He said that the “rate of adverse events with pembrolizumab was low, especially in the adjuvant setting.”

Following his presentation, Dr. Schmid was asked whether he would consider retrying immunotherapy in patients after progression on pembrolizumab.

He replied that this is currently a “data-free zone.”

However, he said: “If a patient responded immunotherapy initially, had a disease-free interval and then has recurrence, then I would consider, if the patient is PD-L1 [programmed death–ligand 1] positive, at that time to add immunotherapy. We can’t say whether those patients will derive the same benefit” as that seen in randomized controlled trials in later stage TNBC, he added, “but there is, in my opinion, little to lose, especially if we have already established the patient tolerates immunotherapy well in that setting.”

Dr. Schmid continued that he “personally found it reassuring” that, in the current study, even patients without a complete pathological response “still showed a substantially better event-free survival compared to patients without immunotherapy, so I personally would consider immunotherapy for those patients when they relapse but we can discuss what the optimal disease-free interval is.”

The study was funded by Merck Sharp and Dohme. Both Dr. Rugo and Dr. Schmid reported relationships numerous pharmaceutical companies.

.

The benefit of giving pembolizumab (Keytruda, Merck) in the neoadjuvant and adjuvant setting to patients with early triple-negative breast cancer (TNBC) extends across subgroups and clinical situations, suggests the latest analysis from KEYNOTE-522.

The original trial data in more than 1,100 patients with early-stage TNBC indicated that adding pembrolizumab to chemotherapy prior to surgery and giving the drug for a year afterward improves event-free survival (EFS) over placebo by 37%.

Now, the researchers conducted a series of prespecified sensitivity and subgroup analyses, finding remarkably consistent EFS outcomes whether considering the addition of adjuvant chemotherapy, positive surgical margins, or disease characteristics such as nodal status and disease stage.

The analyses showed that the benefit with pembrolizumab over placebo was “robust,” said study presenter Peter Schmid, MD, PhD, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London.

“These results further support pembrolizumab plus platinum-containing neoadjuvant chemotherapy followed by adjuvant pembrolizumab after surgery as a new standard of care treatment regimen for patients with high-risk, early-stage TNBC,” he said.

The research was presented at the San Antonio Breast Cancer Symposium on Dec. 7.

Hope S. Rugo, MD, who was invited to comment on the findings, noted that, while the sensitivity analyses showed the benefit with pembrolizumab was seen across the board, the numbers in each group of interest were “very small, making any impact unlikely.”

She continued that there also remain a number of unanswered questions, chief among them being: “Does everybody need a checkpoint inhibitor? Perhaps studies ... could help us understand which patients might do well with chemotherapy alone.”

Dr. Rugo, who is professor of medicine in the division of hematology and oncology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, , added that “we need to understand the balance of risk and toxicity” asking whether there are patients whose risk of an immunotoxicity is “so high that we should not give them a checkpoint inhibitor.”

It is not clear what constitutes the optimal chemotherapy backbone. “Does everybody need carboplatin? Does everyone need a year of pembrolizumab, even with a pathologic complete response given the intriguing data from GeparNUEVO and previously the I-SPY trial?” she asked.

“Of course, we don’t know the answers to those questions,” she said, but it is nevertheless possible to draw a roadmap for the treatment of early TNBC, although the choice of adjuvant therapy following surgery is less clear.

Dr. Rugo conducted a Twitter poll to canvas opinion on what to give to patients following surgery, depending on whether or not they have a pathological complete response.

At 73%, most of almost 200 respondents said patients with a pathological complete response should continue pembrolizumab for 1 year, while 72% said that patients without a pathological complete response should receive combination therapy of pembrolizumab and either capecitabine or olaparib, depending on mutational status.

Dr. Schmid began his presentation by noting that KEYNOTE-522 was the first prospective, randomized, phase 3 trial of pembrolizumab in early TNBC in the neoadjuvant and adjuvant setting.

Previously presented results showed that adding neoadjuvant pembrolizumab to chemotherapy was associated with a clinically meaningful increase in pathological complete response, while continuing with adjuvant chemotherapy after surgery led to a clinically meaningful improvement in EFS.

Consequently, the Food and Drug Administration approved pembrolizumab in this setting for patients with high-risk early-stage TNBC.

He reminded the audience that the trial included 1,174 patients randomized 2:1 to pembrolizumab or placebo every 3 weeks alongside eight cycles of chemotherapy, followed by pembrolizumab over placebo alone for up to nine cycles after undergoing definitive surgery.

After a median follow-up of 39.1 months, 15.7% of patients treated with pembrolizumab experienced an event versus 23.9% of those in the placebo group, at a hazard ratio of 0.63 (P = .00031). At 36 months, the EFS rate was 84.5% with pembrolizumab and 76.8% in patients treated with placebo.

Dr. Schmid said that they then performed five prespecified sensitivity analyses, which revealed that the results were “consistent with the primary EFS in all five sensitivity analyses, showing the robustnesses of the event-free survival benefit in the pembrolizumab arm.”

The first analysis, he continued, is of “particular interest as it considered the impact of postsurgery new anticancer therapy. For example, the use of adjuvant capecitabine.”

Censoring 31 patients from the pembrolizumab arm who received the drug and 13 of those given placebo, the team found that the hazard ratio for EFS for pembrolizumab versus placebo was 0.64.

Removing “positive margin at last surgery” as part of the definition of EFS also did not change the results substantially, with the HR for EFS for pembrolizumab versus placebo at 0.65.

Subgroup analysis revealed “consistent EFS results,” Dr. Schmid said, irrespective of whether stratifying the patients by nodal status, overall disease stage, menopausal status, HER2 status, or lactate dehydrogenase levels.

While patients in both treatment arms who had nodal involvement had worse outcomes than those without, those in the pembrolizumab arm “still had improved outcomes, compared with placebo, suggesting that it provides benefit regardless of nodal status.”

“Similarly, the EFS benefit with pembrolizumab was irrespective of disease stage,” Dr. Schmid said. Although the EFS improvement was greater in patients with stage II rather than III disease, at a HR of 0.60 versus 0.68, it highlights “the importance of early intervention.”

He said that the “rate of adverse events with pembrolizumab was low, especially in the adjuvant setting.”

Following his presentation, Dr. Schmid was asked whether he would consider retrying immunotherapy in patients after progression on pembrolizumab.

He replied that this is currently a “data-free zone.”

However, he said: “If a patient responded immunotherapy initially, had a disease-free interval and then has recurrence, then I would consider, if the patient is PD-L1 [programmed death–ligand 1] positive, at that time to add immunotherapy. We can’t say whether those patients will derive the same benefit” as that seen in randomized controlled trials in later stage TNBC, he added, “but there is, in my opinion, little to lose, especially if we have already established the patient tolerates immunotherapy well in that setting.”

Dr. Schmid continued that he “personally found it reassuring” that, in the current study, even patients without a complete pathological response “still showed a substantially better event-free survival compared to patients without immunotherapy, so I personally would consider immunotherapy for those patients when they relapse but we can discuss what the optimal disease-free interval is.”

The study was funded by Merck Sharp and Dohme. Both Dr. Rugo and Dr. Schmid reported relationships numerous pharmaceutical companies.

.

The benefit of giving pembolizumab (Keytruda, Merck) in the neoadjuvant and adjuvant setting to patients with early triple-negative breast cancer (TNBC) extends across subgroups and clinical situations, suggests the latest analysis from KEYNOTE-522.

The original trial data in more than 1,100 patients with early-stage TNBC indicated that adding pembrolizumab to chemotherapy prior to surgery and giving the drug for a year afterward improves event-free survival (EFS) over placebo by 37%.

Now, the researchers conducted a series of prespecified sensitivity and subgroup analyses, finding remarkably consistent EFS outcomes whether considering the addition of adjuvant chemotherapy, positive surgical margins, or disease characteristics such as nodal status and disease stage.

The analyses showed that the benefit with pembrolizumab over placebo was “robust,” said study presenter Peter Schmid, MD, PhD, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London.

“These results further support pembrolizumab plus platinum-containing neoadjuvant chemotherapy followed by adjuvant pembrolizumab after surgery as a new standard of care treatment regimen for patients with high-risk, early-stage TNBC,” he said.

The research was presented at the San Antonio Breast Cancer Symposium on Dec. 7.

Hope S. Rugo, MD, who was invited to comment on the findings, noted that, while the sensitivity analyses showed the benefit with pembrolizumab was seen across the board, the numbers in each group of interest were “very small, making any impact unlikely.”

She continued that there also remain a number of unanswered questions, chief among them being: “Does everybody need a checkpoint inhibitor? Perhaps studies ... could help us understand which patients might do well with chemotherapy alone.”

Dr. Rugo, who is professor of medicine in the division of hematology and oncology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, , added that “we need to understand the balance of risk and toxicity” asking whether there are patients whose risk of an immunotoxicity is “so high that we should not give them a checkpoint inhibitor.”

It is not clear what constitutes the optimal chemotherapy backbone. “Does everybody need carboplatin? Does everyone need a year of pembrolizumab, even with a pathologic complete response given the intriguing data from GeparNUEVO and previously the I-SPY trial?” she asked.

“Of course, we don’t know the answers to those questions,” she said, but it is nevertheless possible to draw a roadmap for the treatment of early TNBC, although the choice of adjuvant therapy following surgery is less clear.

Dr. Rugo conducted a Twitter poll to canvas opinion on what to give to patients following surgery, depending on whether or not they have a pathological complete response.

At 73%, most of almost 200 respondents said patients with a pathological complete response should continue pembrolizumab for 1 year, while 72% said that patients without a pathological complete response should receive combination therapy of pembrolizumab and either capecitabine or olaparib, depending on mutational status.

Dr. Schmid began his presentation by noting that KEYNOTE-522 was the first prospective, randomized, phase 3 trial of pembrolizumab in early TNBC in the neoadjuvant and adjuvant setting.

Previously presented results showed that adding neoadjuvant pembrolizumab to chemotherapy was associated with a clinically meaningful increase in pathological complete response, while continuing with adjuvant chemotherapy after surgery led to a clinically meaningful improvement in EFS.

Consequently, the Food and Drug Administration approved pembrolizumab in this setting for patients with high-risk early-stage TNBC.

He reminded the audience that the trial included 1,174 patients randomized 2:1 to pembrolizumab or placebo every 3 weeks alongside eight cycles of chemotherapy, followed by pembrolizumab over placebo alone for up to nine cycles after undergoing definitive surgery.

After a median follow-up of 39.1 months, 15.7% of patients treated with pembrolizumab experienced an event versus 23.9% of those in the placebo group, at a hazard ratio of 0.63 (P = .00031). At 36 months, the EFS rate was 84.5% with pembrolizumab and 76.8% in patients treated with placebo.

Dr. Schmid said that they then performed five prespecified sensitivity analyses, which revealed that the results were “consistent with the primary EFS in all five sensitivity analyses, showing the robustnesses of the event-free survival benefit in the pembrolizumab arm.”

The first analysis, he continued, is of “particular interest as it considered the impact of postsurgery new anticancer therapy. For example, the use of adjuvant capecitabine.”

Censoring 31 patients from the pembrolizumab arm who received the drug and 13 of those given placebo, the team found that the hazard ratio for EFS for pembrolizumab versus placebo was 0.64.

Removing “positive margin at last surgery” as part of the definition of EFS also did not change the results substantially, with the HR for EFS for pembrolizumab versus placebo at 0.65.

Subgroup analysis revealed “consistent EFS results,” Dr. Schmid said, irrespective of whether stratifying the patients by nodal status, overall disease stage, menopausal status, HER2 status, or lactate dehydrogenase levels.

While patients in both treatment arms who had nodal involvement had worse outcomes than those without, those in the pembrolizumab arm “still had improved outcomes, compared with placebo, suggesting that it provides benefit regardless of nodal status.”

“Similarly, the EFS benefit with pembrolizumab was irrespective of disease stage,” Dr. Schmid said. Although the EFS improvement was greater in patients with stage II rather than III disease, at a HR of 0.60 versus 0.68, it highlights “the importance of early intervention.”

He said that the “rate of adverse events with pembrolizumab was low, especially in the adjuvant setting.”

Following his presentation, Dr. Schmid was asked whether he would consider retrying immunotherapy in patients after progression on pembrolizumab.

He replied that this is currently a “data-free zone.”

However, he said: “If a patient responded immunotherapy initially, had a disease-free interval and then has recurrence, then I would consider, if the patient is PD-L1 [programmed death–ligand 1] positive, at that time to add immunotherapy. We can’t say whether those patients will derive the same benefit” as that seen in randomized controlled trials in later stage TNBC, he added, “but there is, in my opinion, little to lose, especially if we have already established the patient tolerates immunotherapy well in that setting.”

Dr. Schmid continued that he “personally found it reassuring” that, in the current study, even patients without a complete pathological response “still showed a substantially better event-free survival compared to patients without immunotherapy, so I personally would consider immunotherapy for those patients when they relapse but we can discuss what the optimal disease-free interval is.”

The study was funded by Merck Sharp and Dohme. Both Dr. Rugo and Dr. Schmid reported relationships numerous pharmaceutical companies.

.