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.

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

Key clinical point: Compared with fulvestrant alone, addition of sapanisertib to fulvestrant led to numerical but not statistically significant improvement in progression-free survival (PFS) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC), but with increased toxicity.

Major finding: Median PFS was 3.5 months with only fulvestrant vs 7.2 months with fulvestrant+sapanisertib daily (QD; hazard ratio [HR], 0.77; 95% CI, 0.47-1.26) and 5.6 months with fulvestrant+sapanisertib weekly (QW; HR, 0.88; 95% CI, 0.53-1.45) arms. Fulvestrant+sapanisertib vs fulvestrant alone was associated with higher grade ≥3 treatment-related treatment-emergent adverse events (>50% vs none).

Study details: Findings are from a phase 2 study including 141 postmenopausal women with ER+/HER2− advanced or metastatic BC who were randomly assigned to fulvestrant, fulvestrant+sapanisertib QD, or fulvestrant+sapanisertib QW.

Disclosures: This study was funded by Millennium Pharmaceuticals. The authors declared serving in the advisory committee and speaker’s bureau and/or receiving consulting fees, grants, funds, honoraria, and travel expenses from Millennium Pharmaceuticals and other sources. Five authors declared being employees and/or shareholders of Millennium Pharmaceuticals.

Source: García-Sáenz JÁ et al. Clin Cancer Res. 2022 Jan 3. doi: 10.1158/1078-0432.CCR-21-2652.

Key clinical point: Compared with fulvestrant alone, addition of sapanisertib to fulvestrant led to numerical but not statistically significant improvement in progression-free survival (PFS) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC), but with increased toxicity.

Major finding: Median PFS was 3.5 months with only fulvestrant vs 7.2 months with fulvestrant+sapanisertib daily (QD; hazard ratio [HR], 0.77; 95% CI, 0.47-1.26) and 5.6 months with fulvestrant+sapanisertib weekly (QW; HR, 0.88; 95% CI, 0.53-1.45) arms. Fulvestrant+sapanisertib vs fulvestrant alone was associated with higher grade ≥3 treatment-related treatment-emergent adverse events (>50% vs none).

Study details: Findings are from a phase 2 study including 141 postmenopausal women with ER+/HER2− advanced or metastatic BC who were randomly assigned to fulvestrant, fulvestrant+sapanisertib QD, or fulvestrant+sapanisertib QW.

Disclosures: This study was funded by Millennium Pharmaceuticals. The authors declared serving in the advisory committee and speaker’s bureau and/or receiving consulting fees, grants, funds, honoraria, and travel expenses from Millennium Pharmaceuticals and other sources. Five authors declared being employees and/or shareholders of Millennium Pharmaceuticals.

Source: García-Sáenz JÁ et al. Clin Cancer Res. 2022 Jan 3. doi: 10.1158/1078-0432.CCR-21-2652.

Key clinical point: Compared with fulvestrant alone, addition of sapanisertib to fulvestrant led to numerical but not statistically significant improvement in progression-free survival (PFS) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC), but with increased toxicity.

Major finding: Median PFS was 3.5 months with only fulvestrant vs 7.2 months with fulvestrant+sapanisertib daily (QD; hazard ratio [HR], 0.77; 95% CI, 0.47-1.26) and 5.6 months with fulvestrant+sapanisertib weekly (QW; HR, 0.88; 95% CI, 0.53-1.45) arms. Fulvestrant+sapanisertib vs fulvestrant alone was associated with higher grade ≥3 treatment-related treatment-emergent adverse events (>50% vs none).

Study details: Findings are from a phase 2 study including 141 postmenopausal women with ER+/HER2− advanced or metastatic BC who were randomly assigned to fulvestrant, fulvestrant+sapanisertib QD, or fulvestrant+sapanisertib QW.

Disclosures: This study was funded by Millennium Pharmaceuticals. The authors declared serving in the advisory committee and speaker’s bureau and/or receiving consulting fees, grants, funds, honoraria, and travel expenses from Millennium Pharmaceuticals and other sources. Five authors declared being employees and/or shareholders of Millennium Pharmaceuticals.

Source: García-Sáenz JÁ et al. Clin Cancer Res. 2022 Jan 3. doi: 10.1158/1078-0432.CCR-21-2652.

Key clinical point: With an extended median follow-up of 53.5 months, ribociclib+endocrine therapy (ET) continued to prolong survival vs placebo+ET in pre-/perimenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: Ribociclib vs placebo prolonged the median overall survival in overall population (58.7 months vs 48 months; hazard ratio [HR], 0.76; 95% CI, 0.61-0.96) and in women aged <40 years (51.3 months vs 40.5 months; HR, 0.65; 95% CI, 0.43-0.98). No new safety signals were identified.

Study details: Findings are from an exploratory analysis of phase 3 MONALEESA-7 trial including 672 pre- or perimenopausal women with HR+/HER2− advanced BC who were randomly assigned to ET+ribociclib or ET+placebo.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors reported receiving grants, nonfinancial support, and advisory and personal fees from Novartis and other sources. Six authors declared being employees and shareholders of Novartis.

Source: Lu YS et al. Clin Cancer Res. 2021 Dec 29. doi: 10.1158/1078-0432.CCR-21-3032.

Key clinical point: With an extended median follow-up of 53.5 months, ribociclib+endocrine therapy (ET) continued to prolong survival vs placebo+ET in pre-/perimenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: Ribociclib vs placebo prolonged the median overall survival in overall population (58.7 months vs 48 months; hazard ratio [HR], 0.76; 95% CI, 0.61-0.96) and in women aged <40 years (51.3 months vs 40.5 months; HR, 0.65; 95% CI, 0.43-0.98). No new safety signals were identified.

Study details: Findings are from an exploratory analysis of phase 3 MONALEESA-7 trial including 672 pre- or perimenopausal women with HR+/HER2− advanced BC who were randomly assigned to ET+ribociclib or ET+placebo.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors reported receiving grants, nonfinancial support, and advisory and personal fees from Novartis and other sources. Six authors declared being employees and shareholders of Novartis.

Source: Lu YS et al. Clin Cancer Res. 2021 Dec 29. doi: 10.1158/1078-0432.CCR-21-3032.

Key clinical point: With an extended median follow-up of 53.5 months, ribociclib+endocrine therapy (ET) continued to prolong survival vs placebo+ET in pre-/perimenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: Ribociclib vs placebo prolonged the median overall survival in overall population (58.7 months vs 48 months; hazard ratio [HR], 0.76; 95% CI, 0.61-0.96) and in women aged <40 years (51.3 months vs 40.5 months; HR, 0.65; 95% CI, 0.43-0.98). No new safety signals were identified.

Study details: Findings are from an exploratory analysis of phase 3 MONALEESA-7 trial including 672 pre- or perimenopausal women with HR+/HER2− advanced BC who were randomly assigned to ET+ribociclib or ET+placebo.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors reported receiving grants, nonfinancial support, and advisory and personal fees from Novartis and other sources. Six authors declared being employees and shareholders of Novartis.

Source: Lu YS et al. Clin Cancer Res. 2021 Dec 29. doi: 10.1158/1078-0432.CCR-21-3032.

Key clinical point: Low vs high expression of tumor-specific thyroid hormone receptor alpha-2 (THRα-2) was associated with unfavorable tumor characteristics and higher breast cancer-specific mortality in women with invasive breast cancer.

Major finding: Low vs high THRα-2 expression was associated with estrogen receptor (ER) negativity (odds ratio [OR], 4.04; 95% CI, 2.28-7.15), tumor size of >20-50 mm (OR, 2.20; 95% CI, 1.39-3.49), and high risk for breast cancer-specific mortality in the overall population (hazard ratio [HR], 1.38; 95% CI, 0.96-1.99) and among women with ER-positive tumors (adjusted HR, 1.31; 95% CI, 1.01-1.73).

Study details: Findings are from a follow-up of a population-based cohort, the Malmö Diet and Cancer Study consisting of 17,035 women, of which 654 women with invasive breast cancer and evaluable tumor tissue were included in the present study.

Disclosures: This study was funded by the Swedish Cancer Society, Gunnar Nilsson Cancer Foundation, Ernhold Lundström Foundation, and other sources. The authors declared no conflict of interests.

Source: Sandsveden M et al. Breast Cancer Res. 2021 Dec 20. doi: 10.1186/s13058-021-01496-7.

Key clinical point: Low vs high expression of tumor-specific thyroid hormone receptor alpha-2 (THRα-2) was associated with unfavorable tumor characteristics and higher breast cancer-specific mortality in women with invasive breast cancer.

Major finding: Low vs high THRα-2 expression was associated with estrogen receptor (ER) negativity (odds ratio [OR], 4.04; 95% CI, 2.28-7.15), tumor size of >20-50 mm (OR, 2.20; 95% CI, 1.39-3.49), and high risk for breast cancer-specific mortality in the overall population (hazard ratio [HR], 1.38; 95% CI, 0.96-1.99) and among women with ER-positive tumors (adjusted HR, 1.31; 95% CI, 1.01-1.73).

Study details: Findings are from a follow-up of a population-based cohort, the Malmö Diet and Cancer Study consisting of 17,035 women, of which 654 women with invasive breast cancer and evaluable tumor tissue were included in the present study.

Disclosures: This study was funded by the Swedish Cancer Society, Gunnar Nilsson Cancer Foundation, Ernhold Lundström Foundation, and other sources. The authors declared no conflict of interests.

Source: Sandsveden M et al. Breast Cancer Res. 2021 Dec 20. doi: 10.1186/s13058-021-01496-7.

Key clinical point: Low vs high expression of tumor-specific thyroid hormone receptor alpha-2 (THRα-2) was associated with unfavorable tumor characteristics and higher breast cancer-specific mortality in women with invasive breast cancer.

Major finding: Low vs high THRα-2 expression was associated with estrogen receptor (ER) negativity (odds ratio [OR], 4.04; 95% CI, 2.28-7.15), tumor size of >20-50 mm (OR, 2.20; 95% CI, 1.39-3.49), and high risk for breast cancer-specific mortality in the overall population (hazard ratio [HR], 1.38; 95% CI, 0.96-1.99) and among women with ER-positive tumors (adjusted HR, 1.31; 95% CI, 1.01-1.73).

Study details: Findings are from a follow-up of a population-based cohort, the Malmö Diet and Cancer Study consisting of 17,035 women, of which 654 women with invasive breast cancer and evaluable tumor tissue were included in the present study.

Disclosures: This study was funded by the Swedish Cancer Society, Gunnar Nilsson Cancer Foundation, Ernhold Lundström Foundation, and other sources. The authors declared no conflict of interests.

Source: Sandsveden M et al. Breast Cancer Res. 2021 Dec 20. doi: 10.1186/s13058-021-01496-7.

Key clinical point: In this real-world population, low expression of human epidermal growth factor receptor 2 (HER2) did not affect the prognosis of metastatic breast cancer (BC).

Major finding: HER2-low vs HER2-negative disease had no significant effect on the overall survival, neither in hormone receptor-positive (hazard ratio [HR], 0.89; P = .171) nor in triple-negative (HR, 0.92; P = .585) subgroups.

Study details: Findings are from an analysis of 1,973 patients with metastatic BC from the metastatic BC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT). Among evaluable patients, 20.3% were HER2-positive, 35.2% were HER2-low, and 44.5% were completely HER2-negative.

Disclosures: The AGMT-MBC-registry is supported by grants from Roche, Daiichi Sankyo, Pfizer, and AstraZeneca. The authors declared expert testimony and/or receiving honoraria, research grants, and travel support from several sources.

Source: Gampenrieder SP et al. Breast Cancer Res. 2021 Dec 14. doi: 10.1186/s13058-021-01492-x.

Key clinical point: In this real-world population, low expression of human epidermal growth factor receptor 2 (HER2) did not affect the prognosis of metastatic breast cancer (BC).

Major finding: HER2-low vs HER2-negative disease had no significant effect on the overall survival, neither in hormone receptor-positive (hazard ratio [HR], 0.89; P = .171) nor in triple-negative (HR, 0.92; P = .585) subgroups.

Study details: Findings are from an analysis of 1,973 patients with metastatic BC from the metastatic BC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT). Among evaluable patients, 20.3% were HER2-positive, 35.2% were HER2-low, and 44.5% were completely HER2-negative.

Disclosures: The AGMT-MBC-registry is supported by grants from Roche, Daiichi Sankyo, Pfizer, and AstraZeneca. The authors declared expert testimony and/or receiving honoraria, research grants, and travel support from several sources.

Source: Gampenrieder SP et al. Breast Cancer Res. 2021 Dec 14. doi: 10.1186/s13058-021-01492-x.

Key clinical point: In this real-world population, low expression of human epidermal growth factor receptor 2 (HER2) did not affect the prognosis of metastatic breast cancer (BC).

Major finding: HER2-low vs HER2-negative disease had no significant effect on the overall survival, neither in hormone receptor-positive (hazard ratio [HR], 0.89; P = .171) nor in triple-negative (HR, 0.92; P = .585) subgroups.

Study details: Findings are from an analysis of 1,973 patients with metastatic BC from the metastatic BC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT). Among evaluable patients, 20.3% were HER2-positive, 35.2% were HER2-low, and 44.5% were completely HER2-negative.

Disclosures: The AGMT-MBC-registry is supported by grants from Roche, Daiichi Sankyo, Pfizer, and AstraZeneca. The authors declared expert testimony and/or receiving honoraria, research grants, and travel support from several sources.

Source: Gampenrieder SP et al. Breast Cancer Res. 2021 Dec 14. doi: 10.1186/s13058-021-01492-x.

Key clinical point: Replacing trastuzumab+taxane with trastuzumab emtansine (T-DM1) did not improve survival in high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC).

Major finding: The risk for invasive disease-free survival was not significantly different between trastuzumab+taxane+pertuzumab and T-DM1+pertuzumab arms in the overall population (stratified hazard ratio [sHR], 0.98; 95% CI, 0.72-1.32) and the node-positive subpopulation (sHR, 0.97; 95% CI, 0.71-1.32) along with similar rates of grade 3 or higher and serious adverse events.

Study details: Findings are from the phase 3 KAITLIN study, including 1,846 patients with HER2-positive early BC who were randomly assigned to receive T-DM1+pertuzumab or trastuzumab+taxane+pertuzumab after surgery and anthracycline chemotherapy.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. The authors declared serving as consultant, speaker, and/or receiving honorarium, funding, and travel expense from several sources. Some authors were employed and/or held stocks in various sources.

Source: Krop IE et al. J Clin Oncol. 2021 Dec 10. doi: 10.1200/JCO.21.00896.

Key clinical point: Replacing trastuzumab+taxane with trastuzumab emtansine (T-DM1) did not improve survival in high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC).

Major finding: The risk for invasive disease-free survival was not significantly different between trastuzumab+taxane+pertuzumab and T-DM1+pertuzumab arms in the overall population (stratified hazard ratio [sHR], 0.98; 95% CI, 0.72-1.32) and the node-positive subpopulation (sHR, 0.97; 95% CI, 0.71-1.32) along with similar rates of grade 3 or higher and serious adverse events.

Study details: Findings are from the phase 3 KAITLIN study, including 1,846 patients with HER2-positive early BC who were randomly assigned to receive T-DM1+pertuzumab or trastuzumab+taxane+pertuzumab after surgery and anthracycline chemotherapy.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. The authors declared serving as consultant, speaker, and/or receiving honorarium, funding, and travel expense from several sources. Some authors were employed and/or held stocks in various sources.

Source: Krop IE et al. J Clin Oncol. 2021 Dec 10. doi: 10.1200/JCO.21.00896.

Key clinical point: Replacing trastuzumab+taxane with trastuzumab emtansine (T-DM1) did not improve survival in high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC).

Major finding: The risk for invasive disease-free survival was not significantly different between trastuzumab+taxane+pertuzumab and T-DM1+pertuzumab arms in the overall population (stratified hazard ratio [sHR], 0.98; 95% CI, 0.72-1.32) and the node-positive subpopulation (sHR, 0.97; 95% CI, 0.71-1.32) along with similar rates of grade 3 or higher and serious adverse events.

Study details: Findings are from the phase 3 KAITLIN study, including 1,846 patients with HER2-positive early BC who were randomly assigned to receive T-DM1+pertuzumab or trastuzumab+taxane+pertuzumab after surgery and anthracycline chemotherapy.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. The authors declared serving as consultant, speaker, and/or receiving honorarium, funding, and travel expense from several sources. Some authors were employed and/or held stocks in various sources.

Source: Krop IE et al. J Clin Oncol. 2021 Dec 10. doi: 10.1200/JCO.21.00896.

Key clinical point: Palbociclib+fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-sensitive advanced breast cancer (BC).

Major finding: Palbociclib+fulvestrant vs placebo+fulvestrant improved 1-year PFS (83.5% vs 71.9%) and reduced the risk for progressive disease by 45% (hazard ratio [HR], 0.55; 80% CI, 0.36-0.83). Grade 3 or higher adverse events were reported by 80.9% vs 37.9% of patients in palbociclib/fulvestrant vs placebo/fulvestrant arms.

Study details: This was a phase 2 FLIPPER study of 189 postmenopausal women with HR-positive, HER2-negative, endocrine-sensitive advanced BC who were randomly assigned to palbociclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by GEICAM Spanish Breast Cancer Group, AstraZeneca, and Pfizer. The authors reported receiving research grants, advisory board fees, consulting fees, honoraria, and travel and accommodation support from several sources.

Source: Albanell J et al. Eur J Cancer. 2021 Dec 11. doi: 10.1016/j.ejca.2021.11.010.

Key clinical point: Palbociclib+fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-sensitive advanced breast cancer (BC).

Major finding: Palbociclib+fulvestrant vs placebo+fulvestrant improved 1-year PFS (83.5% vs 71.9%) and reduced the risk for progressive disease by 45% (hazard ratio [HR], 0.55; 80% CI, 0.36-0.83). Grade 3 or higher adverse events were reported by 80.9% vs 37.9% of patients in palbociclib/fulvestrant vs placebo/fulvestrant arms.

Study details: This was a phase 2 FLIPPER study of 189 postmenopausal women with HR-positive, HER2-negative, endocrine-sensitive advanced BC who were randomly assigned to palbociclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by GEICAM Spanish Breast Cancer Group, AstraZeneca, and Pfizer. The authors reported receiving research grants, advisory board fees, consulting fees, honoraria, and travel and accommodation support from several sources.

Source: Albanell J et al. Eur J Cancer. 2021 Dec 11. doi: 10.1016/j.ejca.2021.11.010.

Key clinical point: Palbociclib+fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-sensitive advanced breast cancer (BC).

Major finding: Palbociclib+fulvestrant vs placebo+fulvestrant improved 1-year PFS (83.5% vs 71.9%) and reduced the risk for progressive disease by 45% (hazard ratio [HR], 0.55; 80% CI, 0.36-0.83). Grade 3 or higher adverse events were reported by 80.9% vs 37.9% of patients in palbociclib/fulvestrant vs placebo/fulvestrant arms.

Study details: This was a phase 2 FLIPPER study of 189 postmenopausal women with HR-positive, HER2-negative, endocrine-sensitive advanced BC who were randomly assigned to palbociclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by GEICAM Spanish Breast Cancer Group, AstraZeneca, and Pfizer. The authors reported receiving research grants, advisory board fees, consulting fees, honoraria, and travel and accommodation support from several sources.

Source: Albanell J et al. Eur J Cancer. 2021 Dec 11. doi: 10.1016/j.ejca.2021.11.010.

Key clinical point: Women with metastatic breast cancer (BC) with long-term response to first-line human epidermal growth factor receptor 2 (HER2)-targeted therapy who achieved no evidence of disease (NED) showed improved survival than those with residual disease (RES).

Major finding: Women with NED vs RES achieved longer median progression-free survival (not reached vs 3.08 years; P < .001) and superior overall survival (not reached vs 5.38 years; P < .001) with premenopausal status (P = .006) and de novo metastases (P = .002) associated with higher chances of achieving NED.

Study details: Findings are from a retrospective study including 103 women with HER2-positive metastatic BC who received first-line chemotherapy+trastuzumab or taxane+trastuzumab+pertuzumab and showed a response duration ≥2-fold higher than those observed in pivotal trials.

Disclosures: This study did not report any source of funding. The authors declared serving as a member of a trial steering committee and/or receiving honoraria, funding, consultancy, and advisory fees from several sources.

Source: Veitch Z et al. Br J Cancer. 2021 Dec 20. doi: 10.1038/s41416-021-01676-4.

Key clinical point: Women with metastatic breast cancer (BC) with long-term response to first-line human epidermal growth factor receptor 2 (HER2)-targeted therapy who achieved no evidence of disease (NED) showed improved survival than those with residual disease (RES).

Major finding: Women with NED vs RES achieved longer median progression-free survival (not reached vs 3.08 years; P < .001) and superior overall survival (not reached vs 5.38 years; P < .001) with premenopausal status (P = .006) and de novo metastases (P = .002) associated with higher chances of achieving NED.

Study details: Findings are from a retrospective study including 103 women with HER2-positive metastatic BC who received first-line chemotherapy+trastuzumab or taxane+trastuzumab+pertuzumab and showed a response duration ≥2-fold higher than those observed in pivotal trials.

Disclosures: This study did not report any source of funding. The authors declared serving as a member of a trial steering committee and/or receiving honoraria, funding, consultancy, and advisory fees from several sources.

Source: Veitch Z et al. Br J Cancer. 2021 Dec 20. doi: 10.1038/s41416-021-01676-4.

Key clinical point: Women with metastatic breast cancer (BC) with long-term response to first-line human epidermal growth factor receptor 2 (HER2)-targeted therapy who achieved no evidence of disease (NED) showed improved survival than those with residual disease (RES).

Major finding: Women with NED vs RES achieved longer median progression-free survival (not reached vs 3.08 years; P < .001) and superior overall survival (not reached vs 5.38 years; P < .001) with premenopausal status (P = .006) and de novo metastases (P = .002) associated with higher chances of achieving NED.

Study details: Findings are from a retrospective study including 103 women with HER2-positive metastatic BC who received first-line chemotherapy+trastuzumab or taxane+trastuzumab+pertuzumab and showed a response duration ≥2-fold higher than those observed in pivotal trials.

Disclosures: This study did not report any source of funding. The authors declared serving as a member of a trial steering committee and/or receiving honoraria, funding, consultancy, and advisory fees from several sources.

Source: Veitch Z et al. Br J Cancer. 2021 Dec 20. doi: 10.1038/s41416-021-01676-4.

Key clinical point: Addition of tucatinib to trastuzumab and capecitabine continued to improve survival along with good tolerability in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) who progressed on HER2-targeted therapies.

Major finding: Addition of tucatinib to trastuzumab and capecitabine significantly improved overall survival (hazard ratio [HR] for death, 0.73; P = .004) and progression-free survival (HR for disease-progression or death, 0.57; P < .00001) compared with placebo. Rates of grade 3 or higher adverse events (AEs) were similar between treatment arms, with only 5.9% of patients discontinuing treatment because of AEs.

Study details: These are the final outcomes from the phase 2 HER2CLIMB study including 612 patients with HER2-positive metastatic BC who progressed on trastuzumab, pertuzumab, and trastuzumab emtansine and were randomly assigned to tucatinib or placebo, each in combination with trastuzumab and capecitabine.

Disclosures: This work was supported by Seagen Inc. and Merck Sharp & Dohme Corp. Four authors declared being employees of Seagen and other sources, and other authors reported ties with various sources.

Source: Curigliano G et al. Ann Oncol. 2021 Dec 22. doi: 10.1016/j.annonc.2021.12.005.

Key clinical point: Addition of tucatinib to trastuzumab and capecitabine continued to improve survival along with good tolerability in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) who progressed on HER2-targeted therapies.

Major finding: Addition of tucatinib to trastuzumab and capecitabine significantly improved overall survival (hazard ratio [HR] for death, 0.73; P = .004) and progression-free survival (HR for disease-progression or death, 0.57; P < .00001) compared with placebo. Rates of grade 3 or higher adverse events (AEs) were similar between treatment arms, with only 5.9% of patients discontinuing treatment because of AEs.

Study details: These are the final outcomes from the phase 2 HER2CLIMB study including 612 patients with HER2-positive metastatic BC who progressed on trastuzumab, pertuzumab, and trastuzumab emtansine and were randomly assigned to tucatinib or placebo, each in combination with trastuzumab and capecitabine.

Disclosures: This work was supported by Seagen Inc. and Merck Sharp & Dohme Corp. Four authors declared being employees of Seagen and other sources, and other authors reported ties with various sources.

Source: Curigliano G et al. Ann Oncol. 2021 Dec 22. doi: 10.1016/j.annonc.2021.12.005.

Key clinical point: Addition of tucatinib to trastuzumab and capecitabine continued to improve survival along with good tolerability in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) who progressed on HER2-targeted therapies.

Major finding: Addition of tucatinib to trastuzumab and capecitabine significantly improved overall survival (hazard ratio [HR] for death, 0.73; P = .004) and progression-free survival (HR for disease-progression or death, 0.57; P < .00001) compared with placebo. Rates of grade 3 or higher adverse events (AEs) were similar between treatment arms, with only 5.9% of patients discontinuing treatment because of AEs.

Study details: These are the final outcomes from the phase 2 HER2CLIMB study including 612 patients with HER2-positive metastatic BC who progressed on trastuzumab, pertuzumab, and trastuzumab emtansine and were randomly assigned to tucatinib or placebo, each in combination with trastuzumab and capecitabine.

Disclosures: This work was supported by Seagen Inc. and Merck Sharp & Dohme Corp. Four authors declared being employees of Seagen and other sources, and other authors reported ties with various sources.

Source: Curigliano G et al. Ann Oncol. 2021 Dec 22. doi: 10.1016/j.annonc.2021.12.005.