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‘Unlimited’ cancer costs: The Medicare Part D dilemma
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Time-restricted eating may reduce CVD risk after breast cancer
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY: CARDIAC ONCO
Clinical Edge Journal Scan Commentary: Recent Trials in Breast Cancer, June 2022
A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).2 In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.[3]
The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.4 An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
Additional References
- Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
- Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
- Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
- Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003
A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).2 In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.[3]
The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.4 An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
Additional References
- Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
- Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
- Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
- Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003
A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).2 In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.[3]
The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.4 An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
Additional References
- Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
- Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
- Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
- Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003
Metformin bombs in breast cancer in landmark trial
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
Sex hormones linked to breast cancer in men
The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.
“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.
The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.
Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.
Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.
The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).
The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.
Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.
The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.
“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.
The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.
Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.
Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.
The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).
The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.
Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.
The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.
“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.
The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.
Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.
Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.
The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).
The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.
Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.
FROM BREAST CANCER RESEARCH
Male breast cancer risk linked with infertility
, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.
A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.
“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”
The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).
Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
Raised risk with history of male infertility
Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).
In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.
Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.
Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
Potential underlying factors
“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”
Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”
She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.
A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.
The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.
“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.
“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.
“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”
Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”
A version of this article first appeared on Medscape UK.
, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.
A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.
“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”
The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).
Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
Raised risk with history of male infertility
Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).
In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.
Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.
Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
Potential underlying factors
“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”
Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”
She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.
A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.
The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.
“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.
“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.
“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”
Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”
A version of this article first appeared on Medscape UK.
, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.
A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.
“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”
The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).
Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
Raised risk with history of male infertility
Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).
In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.
Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.
Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
Potential underlying factors
“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”
Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”
She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.
A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.
The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.
“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.
“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.
“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”
Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”
A version of this article first appeared on Medscape UK.
FROM BREAST CANCER RESEARCH
Breast cancer: Dose to left anterior descending artery tied to adverse cardiac events
Key clinical point: Patients with left-sided breast cancer (BC) who received radiation doses to the left anterior descending artery (LAD) experienced an elevated risk for adverse cardiac outcomes.
Major finding: Mean dose to LAD was associated with an increased risk for any cardiac event (hazard ratio [HR] 1.09; P = .006) and major cardiac events (HR 1.08; P = .022). Receiver operating characteristics analysis identified 2.8 Gy (area under the curve 0.69) as the mean LAD dose threshold, above which the risk for any cardiac event was higher (P = .001).
Study details: Findings are from a retrospective study of 375 consecutively treated female patients with nonmetastatic, left-sided BC who received breast-conserving surgery/mastectomy and adjuvant radiation therapy.
Disclosures: This study did not receive any funding. The authors declared no conflict of interests.
Source: Zureick AH et al. Dose to the left anterior descending artery correlates with cardiac events following irradiation for breast cancer. Int J Radiat Oncol Biol Phys. 2022 (Apr 24). Doi: 10.1016/j.ijrobp.2022.04.019
Key clinical point: Patients with left-sided breast cancer (BC) who received radiation doses to the left anterior descending artery (LAD) experienced an elevated risk for adverse cardiac outcomes.
Major finding: Mean dose to LAD was associated with an increased risk for any cardiac event (hazard ratio [HR] 1.09; P = .006) and major cardiac events (HR 1.08; P = .022). Receiver operating characteristics analysis identified 2.8 Gy (area under the curve 0.69) as the mean LAD dose threshold, above which the risk for any cardiac event was higher (P = .001).
Study details: Findings are from a retrospective study of 375 consecutively treated female patients with nonmetastatic, left-sided BC who received breast-conserving surgery/mastectomy and adjuvant radiation therapy.
Disclosures: This study did not receive any funding. The authors declared no conflict of interests.
Source: Zureick AH et al. Dose to the left anterior descending artery correlates with cardiac events following irradiation for breast cancer. Int J Radiat Oncol Biol Phys. 2022 (Apr 24). Doi: 10.1016/j.ijrobp.2022.04.019
Key clinical point: Patients with left-sided breast cancer (BC) who received radiation doses to the left anterior descending artery (LAD) experienced an elevated risk for adverse cardiac outcomes.
Major finding: Mean dose to LAD was associated with an increased risk for any cardiac event (hazard ratio [HR] 1.09; P = .006) and major cardiac events (HR 1.08; P = .022). Receiver operating characteristics analysis identified 2.8 Gy (area under the curve 0.69) as the mean LAD dose threshold, above which the risk for any cardiac event was higher (P = .001).
Study details: Findings are from a retrospective study of 375 consecutively treated female patients with nonmetastatic, left-sided BC who received breast-conserving surgery/mastectomy and adjuvant radiation therapy.
Disclosures: This study did not receive any funding. The authors declared no conflict of interests.
Source: Zureick AH et al. Dose to the left anterior descending artery correlates with cardiac events following irradiation for breast cancer. Int J Radiat Oncol Biol Phys. 2022 (Apr 24). Doi: 10.1016/j.ijrobp.2022.04.019
Young age has no prognostic significance in HER2+ early BC
Key clinical point: Young age at diagnosis of human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) was not associated with any detrimental prognostic value and had no effect on the efficacy of adjuvant dual anti-HER2 targeted therapy.
Major finding: Young age had no effect on invasive disease-free survival (adjusted hazard ratio [aHR] 1.07; 95% CI 0.84-1.35), regardless of hormone receptor status (positive: aHR 1.10; 95% CI 0.82-1.44 or negative: aHR 0.99; 95% CI 0.62-1.51) and anti-HER2 treatment administered (chemotherapy+trastuzumab+pertuzumab: aHR 1.20; 95% CI 0.83-1.68 or chemotherapy+trastuzumab+placebo: aHR, 0.99; 95% CI, 0.71-1.35).
Study details: Findings are from the phase 3 APHINITY trial including 768 patients aged ≤40 years with HER2+ early BC who were randomly assigned to receive chemotherapy+trastuzumab+placebo or chemotherapy+trastuzumab+pertuzumab.
Disclosures: The APHINITY trial was supported by F Hoffmann-La Roche Ltd/Genentech. Some authors declared receiving research funding, honoraria, grants, or nonfinancial support or serving as advisors, speakers, or consultants for several sources, including Roche/Genentech.
Source: Lambertini M et al. Impact of age on clinical outcomes and efficacy of adjuvant dual anti-HER2 targeted therapy. J Natl Cancer Inst. 2022 (May 5). Doi: 10.1093/jnci/djac096
Key clinical point: Young age at diagnosis of human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) was not associated with any detrimental prognostic value and had no effect on the efficacy of adjuvant dual anti-HER2 targeted therapy.
Major finding: Young age had no effect on invasive disease-free survival (adjusted hazard ratio [aHR] 1.07; 95% CI 0.84-1.35), regardless of hormone receptor status (positive: aHR 1.10; 95% CI 0.82-1.44 or negative: aHR 0.99; 95% CI 0.62-1.51) and anti-HER2 treatment administered (chemotherapy+trastuzumab+pertuzumab: aHR 1.20; 95% CI 0.83-1.68 or chemotherapy+trastuzumab+placebo: aHR, 0.99; 95% CI, 0.71-1.35).
Study details: Findings are from the phase 3 APHINITY trial including 768 patients aged ≤40 years with HER2+ early BC who were randomly assigned to receive chemotherapy+trastuzumab+placebo or chemotherapy+trastuzumab+pertuzumab.
Disclosures: The APHINITY trial was supported by F Hoffmann-La Roche Ltd/Genentech. Some authors declared receiving research funding, honoraria, grants, or nonfinancial support or serving as advisors, speakers, or consultants for several sources, including Roche/Genentech.
Source: Lambertini M et al. Impact of age on clinical outcomes and efficacy of adjuvant dual anti-HER2 targeted therapy. J Natl Cancer Inst. 2022 (May 5). Doi: 10.1093/jnci/djac096
Key clinical point: Young age at diagnosis of human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) was not associated with any detrimental prognostic value and had no effect on the efficacy of adjuvant dual anti-HER2 targeted therapy.
Major finding: Young age had no effect on invasive disease-free survival (adjusted hazard ratio [aHR] 1.07; 95% CI 0.84-1.35), regardless of hormone receptor status (positive: aHR 1.10; 95% CI 0.82-1.44 or negative: aHR 0.99; 95% CI 0.62-1.51) and anti-HER2 treatment administered (chemotherapy+trastuzumab+pertuzumab: aHR 1.20; 95% CI 0.83-1.68 or chemotherapy+trastuzumab+placebo: aHR, 0.99; 95% CI, 0.71-1.35).
Study details: Findings are from the phase 3 APHINITY trial including 768 patients aged ≤40 years with HER2+ early BC who were randomly assigned to receive chemotherapy+trastuzumab+placebo or chemotherapy+trastuzumab+pertuzumab.
Disclosures: The APHINITY trial was supported by F Hoffmann-La Roche Ltd/Genentech. Some authors declared receiving research funding, honoraria, grants, or nonfinancial support or serving as advisors, speakers, or consultants for several sources, including Roche/Genentech.
Source: Lambertini M et al. Impact of age on clinical outcomes and efficacy of adjuvant dual anti-HER2 targeted therapy. J Natl Cancer Inst. 2022 (May 5). Doi: 10.1093/jnci/djac096
Prognostic factors in male breast cancer with bone metastases
Key clinical point: Age, tumor subtype, surgery, and brain metastasis are independent risk factors for survival in male patients with breast cancer (BC) and bone metastases and should be considered when devising a treatment strategy.
Major finding: Overall survival (OS) and cancer-specific survival (CSS) were significantly lower in patients aged >60 years (hazard ratio [HR] 1.671; P = .014 and HR 1.806; P = .009, respectively), with triple-negative BC (HR 3.029; P = .003 and HR 3.025; P = .004, respectively), and without surgery (HR 1.764; P = .012 and HR 1.734; P = .023, respectively), and with brain metastasis worsening OS (HR 2.045; P = .028) but not CSS (P = .056).
Study details: Findings are from a retrospective study including 207 male patients with BC and bone metastases.
Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.
Source: Zhou X et al. Survival analysis in male breast cancer with bone metastasis based on the SEER database. Front Oncol. 2022;12:659812 (Apr 13). Doi: 10.3389/fonc.2022.659812
Key clinical point: Age, tumor subtype, surgery, and brain metastasis are independent risk factors for survival in male patients with breast cancer (BC) and bone metastases and should be considered when devising a treatment strategy.
Major finding: Overall survival (OS) and cancer-specific survival (CSS) were significantly lower in patients aged >60 years (hazard ratio [HR] 1.671; P = .014 and HR 1.806; P = .009, respectively), with triple-negative BC (HR 3.029; P = .003 and HR 3.025; P = .004, respectively), and without surgery (HR 1.764; P = .012 and HR 1.734; P = .023, respectively), and with brain metastasis worsening OS (HR 2.045; P = .028) but not CSS (P = .056).
Study details: Findings are from a retrospective study including 207 male patients with BC and bone metastases.
Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.
Source: Zhou X et al. Survival analysis in male breast cancer with bone metastasis based on the SEER database. Front Oncol. 2022;12:659812 (Apr 13). Doi: 10.3389/fonc.2022.659812
Key clinical point: Age, tumor subtype, surgery, and brain metastasis are independent risk factors for survival in male patients with breast cancer (BC) and bone metastases and should be considered when devising a treatment strategy.
Major finding: Overall survival (OS) and cancer-specific survival (CSS) were significantly lower in patients aged >60 years (hazard ratio [HR] 1.671; P = .014 and HR 1.806; P = .009, respectively), with triple-negative BC (HR 3.029; P = .003 and HR 3.025; P = .004, respectively), and without surgery (HR 1.764; P = .012 and HR 1.734; P = .023, respectively), and with brain metastasis worsening OS (HR 2.045; P = .028) but not CSS (P = .056).
Study details: Findings are from a retrospective study including 207 male patients with BC and bone metastases.
Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.
Source: Zhou X et al. Survival analysis in male breast cancer with bone metastasis based on the SEER database. Front Oncol. 2022;12:659812 (Apr 13). Doi: 10.3389/fonc.2022.659812
Young women with postpartum breast cancer have worst survival
Key clinical point: A breast cancer (BC) diagnosis within 5 years of childbirth (postpartum BC [PPBC]) was associated with worse prognosis than no childbirth prior to diagnosis (nulliparous BC), with the association being strongest in young women diagnosed at the age of <35 years and in those with stage I disease.
Major finding: Women diagnosed with nulliparous BC vs. PPBC at age of <45 years had better overall survival (hazard ratio [HR] 0.61; 95% CI 0.42-0.87), with the difference being more pronounced in women with stage I tumors (HR 0.30; 95% CI 0.11-0.79) and in women diagnosed at the age of ≤35 years (HR 0.44; 95% CI 0.23-0.84).
Study details: The study evaluated a pooled dataset of 2519 women diagnosed with BC at the age of ≥18 years.
Disclosures: This study was funded by grants from the University of Colorado Cancer Center, National Institutes of Health, and other sources. The authors declared no conflict of interests.
Source: Shagisultanova E et al. Overall survival is the lowest among young women with postpartum breast cancer. Eur J Cancer. 2022;168:119-127 (May 4). Doi: 10.1016/j.ejca.2022.03.014
Key clinical point: A breast cancer (BC) diagnosis within 5 years of childbirth (postpartum BC [PPBC]) was associated with worse prognosis than no childbirth prior to diagnosis (nulliparous BC), with the association being strongest in young women diagnosed at the age of <35 years and in those with stage I disease.
Major finding: Women diagnosed with nulliparous BC vs. PPBC at age of <45 years had better overall survival (hazard ratio [HR] 0.61; 95% CI 0.42-0.87), with the difference being more pronounced in women with stage I tumors (HR 0.30; 95% CI 0.11-0.79) and in women diagnosed at the age of ≤35 years (HR 0.44; 95% CI 0.23-0.84).
Study details: The study evaluated a pooled dataset of 2519 women diagnosed with BC at the age of ≥18 years.
Disclosures: This study was funded by grants from the University of Colorado Cancer Center, National Institutes of Health, and other sources. The authors declared no conflict of interests.
Source: Shagisultanova E et al. Overall survival is the lowest among young women with postpartum breast cancer. Eur J Cancer. 2022;168:119-127 (May 4). Doi: 10.1016/j.ejca.2022.03.014
Key clinical point: A breast cancer (BC) diagnosis within 5 years of childbirth (postpartum BC [PPBC]) was associated with worse prognosis than no childbirth prior to diagnosis (nulliparous BC), with the association being strongest in young women diagnosed at the age of <35 years and in those with stage I disease.
Major finding: Women diagnosed with nulliparous BC vs. PPBC at age of <45 years had better overall survival (hazard ratio [HR] 0.61; 95% CI 0.42-0.87), with the difference being more pronounced in women with stage I tumors (HR 0.30; 95% CI 0.11-0.79) and in women diagnosed at the age of ≤35 years (HR 0.44; 95% CI 0.23-0.84).
Study details: The study evaluated a pooled dataset of 2519 women diagnosed with BC at the age of ≥18 years.
Disclosures: This study was funded by grants from the University of Colorado Cancer Center, National Institutes of Health, and other sources. The authors declared no conflict of interests.
Source: Shagisultanova E et al. Overall survival is the lowest among young women with postpartum breast cancer. Eur J Cancer. 2022;168:119-127 (May 4). Doi: 10.1016/j.ejca.2022.03.014