Closing the Male Breast Cancer Research Gap

 The Missing Men in Breast Cancer Research

Male breast cancer is uncommon, accounting for approximately 1% of breast cancer diagnoses. Its rarity, however, has produced a serious clinical problem: men have historically been excluded from many of the studies used to establish breast cancer treatment standards. As a result, physicians frequently treat men using evidence generated primarily—or sometimes entirely—in women. Many of these treatment principles are biologically reasonable and clinically effective, but important male-specific questions remain incompletely answered.

A 2018 analysis of 426 breast cancer clinical trials conducted between 2000 and 2017 found that 65% explicitly excluded men. Across the trials included in the enrollment analysis, only 0.42% of participants were male. The investigators also found that some exclusions occurred without a clear scientific justification. These findings should not be interpreted to mean that every current recommendation is unreliable. They demonstrate that the strength and directness of the evidence vary considerably. JAMA Oncology

The American Society of Clinical Oncology’s guideline for male breast cancer illustrates this limitation. Its evidence review identified only 26 descriptive reports or observational studies; prospective randomized evidence involving men was extremely limited. Consequently, many recommendations were adapted from research in women and supplemented by expert consensus. Surgery, radiation, chemotherapy, HER2-directed treatment and management of metastatic disease generally follow the same principles used for women because tumors are classified by stage and molecular characteristics—not simply by the patient’s sex. Nevertheless, direct male data are needed to determine whether effectiveness, dosing, toxicity and long-term outcomes are truly equivalent. ASCO guideline

Endocrine therapy is one of the clearest examples. Most male breast cancers are estrogen-receptor positive, making hormone-blocking treatment essential for many patients. ASCO recommends tamoxifen for men with hormone-receptor-positive early breast cancer when endocrine therapy is indicated, generally for an initial five years. Men who remain at high risk and tolerate treatment may be offered an additional five years. If tamoxifen cannot be used, an aromatase inhibitor may be combined with gonadotropin-releasing hormone suppression. An aromatase inhibitor used alone may not suppress estrogen adequately in men because the testes continue to contribute to hormonal production.

These recommendations are clinically rational, but the unanswered questions are substantial. Researchers need better information about optimal treatment duration, comparative effectiveness and male-specific adverse effects. Tamoxifen can cause hot flashes, sexual dysfunction, reduced libido, mood changes, weight changes and an increased risk of blood clots. These effects may lead some men to interrupt or discontinue therapy. Yet male-specific adherence strategies and symptom-management interventions have received far less study than treatment efficacy in women.

The research gap extends into survivorship. Men can experience lymphedema, neuropathy, persistent pain, fatigue, bone loss, infertility, body-image distress, anxiety, depression and fear of recurrence. Mastectomy can alter a man’s relationship with his chest and sense of masculinity, while being treated in environments designed almost exclusively for women may intensify isolation. Without sufficient male participation, researchers cannot accurately measure how frequently these problems occur, which patients are most vulnerable or which interventions offer the greatest benefit.

Representation also matters in genetic medicine. All men diagnosed with breast cancer should be offered genetic counseling and germline genetic testing, according to ASCO. Pathogenic variants—particularly in BRCA2, but also BRCA1 and several other cancer-susceptibility genes—can influence treatment, future cancer surveillance and risk assessment for relatives. Male participation in genomic studies can help clarify whether certain inherited variants, tumor mutations or molecular pathways affect disease behavior and treatment response differently.

There has been meaningful progress. In 2020, the U.S. Food and Drug Administration finalized guidance recommending that men be included in breast cancer drug-development trials unless a scientific reason justifies exclusion. The FDA also recognizes that conventional male-only randomized trials may be difficult because the disease is rare. It therefore supports combining clinical-trial evidence with observational studies, registries, electronic health records and other real-world data when appropriate. FDA guidance

Inclusion alone is not enough. Trial results should report male enrollment, treatment exposure, adverse effects and outcomes separately whenever the numbers permit meaningful analysis. Research networks must also collaborate internationally because no single cancer center is likely to enroll enough men rapidly. Remote participation, decentralized follow-up and partnerships with male breast cancer advocacy organizations may reduce geographical and social barriers.

Men should ask their oncology teams whether an appropriate clinical trial, registry, tissue study or survivorship study is available. Participation is always voluntary, and declining a study should never compromise standard care. Greater participation, however, can help move male breast cancer treatment from reasonable extrapolation toward directly demonstrated evidence. Men are not merely a small subgroup within breast cancer research. They are a clinically distinct population whose treatment experiences, toxicities and survivorship needs deserve to be measured, understood and represented.

References

1. Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849-1863. doi:10.1200/JCO.19.03120
2. Duma N, Hoversten KP, Ruddy KJ. Exclusion of male patients in breast cancer clinical trials. JNCI Cancer Spectr. 2018;2(2):pky018. doi:10.1093/jncics/pky018
3. Corrigan KL, Mainwaring W, Miller AB, et al. Exclusion of men from randomized phase III breast cancer clinical trials. Oncologist. 2020;25(6):e990-e992. doi:10.1634/theoncologist.2019-0871
4. Reinisch M, Seiler S, Hauzenberger T, et al. Efficacy of endocrine therapy for the treatment of breast cancer in men: results from the MALE phase 2 randomized clinical trial. JAMA Oncol. 2021;7(4):565-572. doi:10.1001/jamaoncol.2020.7442
5. Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018;29(2):405-417. doi:10.1093/annonc/mdx651
6. Ruddy KJ, Giobbie-Hurder A, Giordano SH, et al. Quality of life and symptoms in male breast cancer survivors. Breast. 2013;22(2):197-199. doi:10.1016/j.breast.2012.12.014
7. US Food and Drug Administration. Male Breast Cancer: Developing Drugs for Treatment—Guidance for Industry. Published August 2020. Accessed August 30, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/male-breast-cancer-developing-drugs-treatment