Some men with breast cancer may have higher mortality risk
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Key takeaways:
- Men with hormone receptor-positive breast cancer have increased risk for death 20 years after diagnosis.
- Clinical pathologic factors influence severity of risk.
Like women, men with hormone receptor-positive breast cancer have mortality risks that persist 20 years after diagnosis, with age, tumor size and grade, and nodal status playing factors, according to findings published in JAMA Oncology.
The kinetics of risk differed between sexes, however, as men with higher-stage hormone receptor-positive breast cancer had a second hazard peak around 11 years, whereas women have only one high point around year 5.
“One of the things that our study highlights is the need for better adjuvant therapies both for men and women with breast cancer, because the risk is prolonged for both,” José P. Leone, MD, medical oncologist at Dana-Farber Cancer Institute, told Healio.
Background and methodology
Healio previously reported the American Cancer Society estimated there would be 313,510 new breast cancer cases in the U.S. in 2024.
Most of those diagnoses are in women.
Breast cancer in men is much rarer. The American Cancer Society estimated there would be only 2,790 new cases in men this year in the same report, with just 530 deaths.
More than 90% of male breast cancer cases are hormone receptor-positive, according to background information provided by researchers.
Studies in women have shown that mortality risk for hormone receptor-positive breast cancer can persist for 2 decades, but Leone and colleagues could not find any research into risk for men.
“We didn’t expect to see specific differences between men and women, but at the same time, we have no prior solid evidence to guide us on that,” Leone said.
Study investigators used SEER data to conduct a retrospective population-based cohort study.
Men had to be diagnosed with stage I to stage III hormone receptor-positive breast cancer between 1990 and 2008 to be included. The final study cohort comprised 2,836 men (median age, 67 years; 80.5% white).
Breast cancer-specific mortality served as the study’s primary endpoint.
Results and next steps
At a median follow-up of 15.41 years, men with hormone receptor-positive disease had a breast cancer-specific mortality of 12.4% with stage I breast cancer, 26.2% with stage II and 46% with stage III.
Hazard rates also increased with nodal status and tumor grade.
“The prolonged risk that men have overall is similar to what has been previously reported in women in terms of the risk over 20 years,” Leone said.
However, men with stage III disease had two peaks compared with one in women.
In a previous study, Leone and colleagues discovered women have a breast cancer-specific mortality peak of 6% around year 5, which then declined. Men had a similar peak around year 4, but after a small decrease, rose to 7.5% around year 11.
Researchers first hypothesized endocrine therapy could play a role in that difference, but do not believe that will be the case now.
“We feel that if this was due to endocrine therapy, we wouldn’t necessarily see a reduction after the first peak before the occurrence of the second peak,” Leone explained. “We think, instead, we would see more of a continuous risk, and we don’t see that.
Left unanswered is whether differences in tumor biology or tumor senescence between men and women could explain the second peak, or any other “host-related factors,” according to Leone.
“For example, immune differences between men and women, or tumor microenvironment differences between men and women may potentially be responsible for this late occurrence of risk that we see in men that hasn’t been seen in women,” he added. “We don’t know the answer. We need more research.”
Leone also believes research needs to look at adjuvant therapies that may be more effective in men than women.
“I will encourage men with a diagnosis of breast cancer to participate in clinical trials as much as possible, to hopefully learn as much as we can from every patient [and] develop treatment options that are better for men,” he said.
That starts with awareness and education.
“One of the first steps to addressing the problem is first recognizing the issue,” he said. “Awareness about the possibility of men developing breast cancer will play a role in diagnosing men with earlier stages of breast cancer where the risks are much lower, even over 20 years.”
References:
- Leone J, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2023.7194.
- Siegel RL, et al. CA Cancer J Clin. 2024;doi:10.3322/caac.21820.
For more information:
Jose P. Leone, MD, can be reached at josep_leone@dfci.harvard.edu.
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