Breast Cancer

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

New efficacy and safety data from the monarchE study show that chemotherapy administered before treatment with abemaciclib and estrogen therapy, led to a clinically meaningful improvement in invasive disease-free survival and distant relapse-free survival for women with HR-positive, ERBB2-negative, node-positive, early breast cancer at high risk of recurrence.

The study was published earlier this year in JAMA Oncology.

Neoadjuvant chemotherapy is often provided to such patients in hopes of achieving breast-conserving surgery. Although pathologic complete response rates can be higher than 50% after chemotherapy treatment in triple-negative and ERBB2-positive breast cancer, most patients with HR-positive and ERBB2-negative breast cancer have residual tumor at surgery after neoadjuvant chemotherapy, which is associated with an increased risk of recurrence.

Adjuvant estrogen therapy can reduce the risk of recurrence in this population, but a significant hazard remains.

“To our knowledge, abemaciclib is the first agent added to standard adjuvant estrogen therapy that has been shown to reduce the risk of recurrence in patients with HR-positive, ERBB2-negative early breast cancer with residual disease after neoadjuvant chemotherapy,” wrote the authors, who were led by Miguel Martin, MD, PhD, Hospital General Universitario Gregorio Marañon, Spain.

In 2021, Food and Drug Administration approved abemaciclib (Verzenio, Lilly) with endocrine therapy for the treatment of HR-positive/ERBB2-negative, node-positive, high-risk early breast cancer. Their decision was based on data from the monarchE study.

The study is at odds with the previously published Penelope-B study, which found no benefit from treatment with the CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) after 42.8 months of follow-up. The authors suggest that the disparate outcomes may be due to pharmacological differences between the two drugs as well as different dosing schedules: In monarchE, patients received abemaciclib on a continuous basis, while patients in Penelope-B received palbociclib for 21 days, followed by 7 days off. The treatment duration was 2 years in monarchE and 1 year in Penelope-B. Abemaciclib can be dosed continuously because it is a stronger inhibitor of CDK4 versus CDK6 compared to abemaciclib, and in vitro studies suggest that continuous dosing could be a key factor in creating profound inhibition of DNA synthesis.

The monarchE study included 5,637 patients who were randomized to receive standard of care estrogen therapy for 5 years with or without abemaciclib (150 mg, twice per day) for 2 years; 36.5% received abemaciclib. The mean age was 49.9 years; 70.8% were White, 22.8% Asian, and 2.7% Black.

The abemaciclib group had a clinically and statistically significant benefit in invasive disease-free survival (IDFS) (hazard ratio, 0.61; nominal P < .001) and distant relapse-free survival (DRFS) (HR, 0.61; nominal P < .001). At 2 years, DRFS was 89.5% in the abemaciclib group and 82.8% in the estrogen therapy–only group. IDFS was 87.2% and 80.6%, respectively. Patients who underwent neoadjuvant chemotherapy had a similar safety profile to the estrogen therapy–only group, although there was a higher incidence of treatment-emergent adverse events. The most common were diarrhea, infections, neutropenia, and fatigue. The most frequent grade treatment-emergent adverse events (of at least 3) were neutropenia and leucopenia.

The researchers noted that patients who underwent neoadjuvant chemotherapy had a worse prognosis than the intent-to-treat arm, as evidenced by a higher risk of 2-year recurrence (19% versus 11%). Exploratory subgroup analyses revealed that treatment with abemaciclib and estrogen therapy conferred IDFS and DRFS benefits regardless of the pathological tumor size and number of positive axillary lymph nodes.

The study was limited by the fact that it was open label, and the subgroup analyses were not powered to find statistically significant associations.

Dr. Martin has received grants from Eli Lilly, which funded monarchE.

New efficacy and safety data from the monarchE study show that chemotherapy administered before treatment with abemaciclib and estrogen therapy, led to a clinically meaningful improvement in invasive disease-free survival and distant relapse-free survival for women with HR-positive, ERBB2-negative, node-positive, early breast cancer at high risk of recurrence.

The study was published earlier this year in JAMA Oncology.

Neoadjuvant chemotherapy is often provided to such patients in hopes of achieving breast-conserving surgery. Although pathologic complete response rates can be higher than 50% after chemotherapy treatment in triple-negative and ERBB2-positive breast cancer, most patients with HR-positive and ERBB2-negative breast cancer have residual tumor at surgery after neoadjuvant chemotherapy, which is associated with an increased risk of recurrence.

Adjuvant estrogen therapy can reduce the risk of recurrence in this population, but a significant hazard remains.

“To our knowledge, abemaciclib is the first agent added to standard adjuvant estrogen therapy that has been shown to reduce the risk of recurrence in patients with HR-positive, ERBB2-negative early breast cancer with residual disease after neoadjuvant chemotherapy,” wrote the authors, who were led by Miguel Martin, MD, PhD, Hospital General Universitario Gregorio Marañon, Spain.

In 2021, Food and Drug Administration approved abemaciclib (Verzenio, Lilly) with endocrine therapy for the treatment of HR-positive/ERBB2-negative, node-positive, high-risk early breast cancer. Their decision was based on data from the monarchE study.

The study is at odds with the previously published Penelope-B study, which found no benefit from treatment with the CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) after 42.8 months of follow-up. The authors suggest that the disparate outcomes may be due to pharmacological differences between the two drugs as well as different dosing schedules: In monarchE, patients received abemaciclib on a continuous basis, while patients in Penelope-B received palbociclib for 21 days, followed by 7 days off. The treatment duration was 2 years in monarchE and 1 year in Penelope-B. Abemaciclib can be dosed continuously because it is a stronger inhibitor of CDK4 versus CDK6 compared to abemaciclib, and in vitro studies suggest that continuous dosing could be a key factor in creating profound inhibition of DNA synthesis.

The monarchE study included 5,637 patients who were randomized to receive standard of care estrogen therapy for 5 years with or without abemaciclib (150 mg, twice per day) for 2 years; 36.5% received abemaciclib. The mean age was 49.9 years; 70.8% were White, 22.8% Asian, and 2.7% Black.

The abemaciclib group had a clinically and statistically significant benefit in invasive disease-free survival (IDFS) (hazard ratio, 0.61; nominal P < .001) and distant relapse-free survival (DRFS) (HR, 0.61; nominal P < .001). At 2 years, DRFS was 89.5% in the abemaciclib group and 82.8% in the estrogen therapy–only group. IDFS was 87.2% and 80.6%, respectively. Patients who underwent neoadjuvant chemotherapy had a similar safety profile to the estrogen therapy–only group, although there was a higher incidence of treatment-emergent adverse events. The most common were diarrhea, infections, neutropenia, and fatigue. The most frequent grade treatment-emergent adverse events (of at least 3) were neutropenia and leucopenia.

The researchers noted that patients who underwent neoadjuvant chemotherapy had a worse prognosis than the intent-to-treat arm, as evidenced by a higher risk of 2-year recurrence (19% versus 11%). Exploratory subgroup analyses revealed that treatment with abemaciclib and estrogen therapy conferred IDFS and DRFS benefits regardless of the pathological tumor size and number of positive axillary lymph nodes.

The study was limited by the fact that it was open label, and the subgroup analyses were not powered to find statistically significant associations.

Dr. Martin has received grants from Eli Lilly, which funded monarchE.

New efficacy and safety data from the monarchE study show that chemotherapy administered before treatment with abemaciclib and estrogen therapy, led to a clinically meaningful improvement in invasive disease-free survival and distant relapse-free survival for women with HR-positive, ERBB2-negative, node-positive, early breast cancer at high risk of recurrence.

The study was published earlier this year in JAMA Oncology.

Neoadjuvant chemotherapy is often provided to such patients in hopes of achieving breast-conserving surgery. Although pathologic complete response rates can be higher than 50% after chemotherapy treatment in triple-negative and ERBB2-positive breast cancer, most patients with HR-positive and ERBB2-negative breast cancer have residual tumor at surgery after neoadjuvant chemotherapy, which is associated with an increased risk of recurrence.

Adjuvant estrogen therapy can reduce the risk of recurrence in this population, but a significant hazard remains.

“To our knowledge, abemaciclib is the first agent added to standard adjuvant estrogen therapy that has been shown to reduce the risk of recurrence in patients with HR-positive, ERBB2-negative early breast cancer with residual disease after neoadjuvant chemotherapy,” wrote the authors, who were led by Miguel Martin, MD, PhD, Hospital General Universitario Gregorio Marañon, Spain.

In 2021, Food and Drug Administration approved abemaciclib (Verzenio, Lilly) with endocrine therapy for the treatment of HR-positive/ERBB2-negative, node-positive, high-risk early breast cancer. Their decision was based on data from the monarchE study.

The study is at odds with the previously published Penelope-B study, which found no benefit from treatment with the CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) after 42.8 months of follow-up. The authors suggest that the disparate outcomes may be due to pharmacological differences between the two drugs as well as different dosing schedules: In monarchE, patients received abemaciclib on a continuous basis, while patients in Penelope-B received palbociclib for 21 days, followed by 7 days off. The treatment duration was 2 years in monarchE and 1 year in Penelope-B. Abemaciclib can be dosed continuously because it is a stronger inhibitor of CDK4 versus CDK6 compared to abemaciclib, and in vitro studies suggest that continuous dosing could be a key factor in creating profound inhibition of DNA synthesis.

The monarchE study included 5,637 patients who were randomized to receive standard of care estrogen therapy for 5 years with or without abemaciclib (150 mg, twice per day) for 2 years; 36.5% received abemaciclib. The mean age was 49.9 years; 70.8% were White, 22.8% Asian, and 2.7% Black.

The abemaciclib group had a clinically and statistically significant benefit in invasive disease-free survival (IDFS) (hazard ratio, 0.61; nominal P < .001) and distant relapse-free survival (DRFS) (HR, 0.61; nominal P < .001). At 2 years, DRFS was 89.5% in the abemaciclib group and 82.8% in the estrogen therapy–only group. IDFS was 87.2% and 80.6%, respectively. Patients who underwent neoadjuvant chemotherapy had a similar safety profile to the estrogen therapy–only group, although there was a higher incidence of treatment-emergent adverse events. The most common were diarrhea, infections, neutropenia, and fatigue. The most frequent grade treatment-emergent adverse events (of at least 3) were neutropenia and leucopenia.

The researchers noted that patients who underwent neoadjuvant chemotherapy had a worse prognosis than the intent-to-treat arm, as evidenced by a higher risk of 2-year recurrence (19% versus 11%). Exploratory subgroup analyses revealed that treatment with abemaciclib and estrogen therapy conferred IDFS and DRFS benefits regardless of the pathological tumor size and number of positive axillary lymph nodes.

The study was limited by the fact that it was open label, and the subgroup analyses were not powered to find statistically significant associations.

Dr. Martin has received grants from Eli Lilly, which funded monarchE.

Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.

But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.

The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).

There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.

The finding was published in the Journal of the National Cancer Institute.

“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.

The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.

The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.

“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
 

Differences between endocrine therapies

“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.

They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.

Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.

Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
 

Study details

Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.

The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.

Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.

Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.

The investigators then analyzed the risk for recurrence in various subgroups.

The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.

Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.

Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.

The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.

The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.

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

Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.

But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.

The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).

There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.

The finding was published in the Journal of the National Cancer Institute.

“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.

The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.

The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.

“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
 

Differences between endocrine therapies

“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.

They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.

Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.

Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
 

Study details

Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.

The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.

Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.

Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.

The investigators then analyzed the risk for recurrence in various subgroups.

The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.

Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.

Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.

The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.

The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.

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

Women with breast cancer who are taking adjuvant endocrine therapy to reduce the risk for recurrence often report that the side effects of dampening down estrogen, such as hot flashes and vaginal dryness, spoil their quality of life, and these side effects can lead to discontinuation of therapy.

But medical measures to address these side effects carry risks, as shown in the results of a new study from Denmark.

The use of vaginal estrogen therapy (VET) increased the risk for breast cancer recurrence by 39% in women with early estrogen receptor–positive breast cancer who were taking aromatase inhibitors (AIs).

There was no increase in the risk for recurrence in women who were using VET and taking tamoxifen or in women who were using VET and not taking any adjuvant endocrine therapy.

The finding was published in the Journal of the National Cancer Institute.

“Patients who are taking aromatase inhibitors should try alternative strategies for management of genitourinary symptoms because (VET) will likely increase their risk for breast cancer recurrence,” warn the authors of an accompanying editorial, Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, oncologists at the Mayo Clinic, Rochester, Minn.

The use of oral estrogen treatment, known as menopausal hormone therapy (MHT), is also not recommended in breast cancer survivors being treated with AIs, the editorialists added.

The study did not find an increase in the risk for recurrence with MHT added onto AIs, but that finding comes from a very small subgroup of only 37 women.

“The absence of an obvious detrimental impact of MHT on breast cancer recurrence or mortality” in this study “is not particularly reassuring,” especially given higher systemic estrogen levels seen with MHT, Dr. Cathcart-Rake and Dr. Ruddy commented.
 

Differences between endocrine therapies

“Our study is, to our knowledge, the first to report a potential increased risk of recurrence in patients receiving AIs treated with VET,” say the investigators, led by Søren Cold, MD, an oncology researcher at Odense University Hospital, Denmark.

They suggest that women who are taking VET and AIs should be switched to tamoxifen after 2-3 years.

Speculating as to the apparent safety differences between the two endocrine therapies, Dr. Cold and colleagues explained that “AIs lower or nearly eliminate estrogen. As such, even a modest increase in circulating estrogens may” increase recurrence risk.

Tamoxifen, on the other hand, competes for estrogen receptor binding, so “a modest elevation of the very low serum estrogen levels” with hormone therapy “is not assumed to counteract the receptor blockade,” they said.
 

Study details

Study participants, obtained from a nationwide registry in Denmark, were diagnosed with early-stage, invasive, estrogen receptor–positive breast cancer from 1997 to 2004. Upfront treatment included surgery plus, in the majority of women, radiation.

The review identified 8,461 such women. After initial treatment for breast cancer, 2,410 went on to adjuvant endocrine therapy, including 2,007 with tamoxifen and 403 with an AI.

Across the entire study population, nearly 2,000 women took VET and 133 women took MHT, as assessed by having redeemed at least two prescriptions. The hormone therapies were used in women who were both on and those who were not on endocrine therapy.

Overall, breast cancer recurred in 1,333 women (16%) over a median follow-up of 9.8 years.

The investigators then analyzed the risk for recurrence in various subgroups.

The 39% higher risk for recurrence was found among the 822 women who used VET while taking an AI, compared with 2,520 women who received AIs alone.

Findings in the study were adjusted for numerous potential confounders, including age, tumor biology, and comorbidities.

Women were a median of 61 years of age (range, 35-91 years). Seventy-seven percent had invasive ductal carcinoma, and 43% were node-positive. Women on hormone therapy tended to be younger, have smaller tumors, and be less likely to have lymph node metastases.

The investigators excluded women who had taken hormone replacement before their breast cancer diagnosis.

The work was funded by the Danish Cancer Society. Dr. Cold reports no disclosures, but some co-authors reported relationships with Samsung, Novartis, Pfizer, and other companies. Dr. Cathcart-Rake and Dr. Ruddy report no disclosures.

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

Key clinical point: In clinically fit older women with breast cancer (BC), high interleukin-6 (IL-6) and C-reactive protein (CRP) levels before chemotherapy treatment may predict chemotherapy-induced deterioration in frailty status.

Major finding: Overall, 25.8% of patients experienced a decline in frailty status due to chemotherapy. Higher vs lower prechemotherapy levels of both IL-6 and CRP were associated with increased odds of decline in frailty status (odds ratio 3.52; P = .003).

Study details: Findings are from a prospective study, The Hurria Older Patients with BC Study, including 295 robust women with stage I-III BC who received chemotherapy.

Disclosures: This study was supported by the National Institute on Aging and other sources. Three authors declared receiving research funding or royalties, owning patents, or holding stock options in pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ji J, Sun C-L, et al. Inflammation and clinical decline after adjuvant chemotherapy in older adults with breast cancer: Results from The Hurria Older Patients prospective study. J Clin Oncol. 2022 (Sep 20). Doi: 10.1200/JCO.22.01217

Key clinical point: In clinically fit older women with breast cancer (BC), high interleukin-6 (IL-6) and C-reactive protein (CRP) levels before chemotherapy treatment may predict chemotherapy-induced deterioration in frailty status.

Major finding: Overall, 25.8% of patients experienced a decline in frailty status due to chemotherapy. Higher vs lower prechemotherapy levels of both IL-6 and CRP were associated with increased odds of decline in frailty status (odds ratio 3.52; P = .003).

Study details: Findings are from a prospective study, The Hurria Older Patients with BC Study, including 295 robust women with stage I-III BC who received chemotherapy.

Disclosures: This study was supported by the National Institute on Aging and other sources. Three authors declared receiving research funding or royalties, owning patents, or holding stock options in pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ji J, Sun C-L, et al. Inflammation and clinical decline after adjuvant chemotherapy in older adults with breast cancer: Results from The Hurria Older Patients prospective study. J Clin Oncol. 2022 (Sep 20). Doi: 10.1200/JCO.22.01217

Key clinical point: In clinically fit older women with breast cancer (BC), high interleukin-6 (IL-6) and C-reactive protein (CRP) levels before chemotherapy treatment may predict chemotherapy-induced deterioration in frailty status.

Major finding: Overall, 25.8% of patients experienced a decline in frailty status due to chemotherapy. Higher vs lower prechemotherapy levels of both IL-6 and CRP were associated with increased odds of decline in frailty status (odds ratio 3.52; P = .003).

Study details: Findings are from a prospective study, The Hurria Older Patients with BC Study, including 295 robust women with stage I-III BC who received chemotherapy.

Disclosures: This study was supported by the National Institute on Aging and other sources. Three authors declared receiving research funding or royalties, owning patents, or holding stock options in pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ji J, Sun C-L, et al. Inflammation and clinical decline after adjuvant chemotherapy in older adults with breast cancer: Results from The Hurria Older Patients prospective study. J Clin Oncol. 2022 (Sep 20). Doi: 10.1200/JCO.22.01217