Male breast cancer: can we still rely on extrapolating data from women?

Breast cancer is overwhelmingly associated with women. Yet around 1% of breast cancers occur in men, and incidence has increased over recent decades. Despite this, male-specific data remain scarce. As a result, management still relies heavily on recommendations and clinical trials conducted in women.

A review published in The Oncologist in 2026 summarizes the available evidence and raises a central question: to what extent can practices established in female breast cancer truly be extrapolated to men?

1. A rare cancer with some distinctive features

Male breast cancer accounts for approximately 1% of all breast cancers and 0.3% of newly diagnosed cancers in men. Its incidence remains low, although it has steadily increased. Diagnosis also tends to occur slightly later than in women, at a median age of 64–65 years.

Genetic predisposition plays an important role. In a series of 708 patients, 18.1% carried a pathogenic variant in a breast cancer susceptibility gene. BRCA2 was by far the most common, found in 11% of patients.

Other risk factors include conditions associated with hormonal imbalance and increased estrogen exposure, such as obesity, liver disease, and Klinefelter syndrome.

2. Predominantly hormone receptor-positive tumors

Male breast cancer has a relatively characteristic tumor profile: the vast majority of tumors are ductal and hormone receptor-positive.

In a cohort of 10,873 men, 88.7% of tumors were ER-positive, 80% were PR-positive, and 5.8% were HER2-positive. Luminal subtypes therefore predominate.

Molecular data, however, remain much more limited. Alterations in PIK3CA and GATA3 have been reported, but available sample sizes are too small to establish clear biological differences between male and female breast cancers.

3. A later diagnosis

As noted above, another important difference is the later diagnosis of breast cancer in men.

The most common presenting symptom is a painless breast mass, usually located in the retroareolar region. Yet in some male cohorts, the median interval between the first symptoms and diagnosis ranged from 4.5 to 12 months, compared with a few days to a few weeks in the female cohorts cited in the review.

At diagnosis, men therefore tend to have larger tumors, more frequent lymph node involvement, and slightly higher rates of distant metastases. Limited awareness of this rare disease may contribute to this diagnostic delay.

4. Treatments still largely modeled on those used in women

In clinical practice, most treatment strategies are still extrapolated from female breast cancer.

Surgery generally follows the same principles, although mastectomy is much more common in men, particularly because of smaller breast volume and the frequent retroareolar location of tumors.

Radiotherapy also follows recommendations established for women but remains underused in men.

A similar pattern is seen with endocrine therapy: for hormone receptor-positive disease, tamoxifen remains the standard endocrine treatment, but it is used less often in men than in women despite observed benefits in disease-free survival and recurrence risk.

Finally, aromatase inhibitors are not recommended as monotherapy in men, partly because they do not sufficiently suppress testicular estrogen production. When used, they should be combined with a GnRH analogue.

5. Another challenge: staying on treatment

Prescribing endocrine therapy is not enough: patients also need to be able to remain on treatment.

Hot flashes, sexual dysfunction, decreased libido, mood disturbances, and musculoskeletal symptoms can affect quality of life. In a large SEER-Medicare cohort, 48.3% of patients had discontinued tamoxifen before completing five years of treatment.

This is far from a minor issue: the available data highlight both the underuse of recommended treatments and high rates of endocrine therapy discontinuation as two potentially modifiable problems in the management of male breast cancer.

6. Targeted therapies: men are almost absent from clinical trials

This is perhaps one of the most striking findings of the review.

Men generally accounted for less than 1–2% of participants in recent major phase III breast cancer trials. Some major trials did not allow men to participate at all.

CDK4/6 inhibitors and therapies targeting HER2, PD-L1, PIK3CA, or germline BRCA mutations are therefore used in men largely on the basis of data obtained in women. This extrapolation is considered reasonable in the absence of alternatives, but it does not allow formal assessment of potential sex-related differences in efficacy or safety.

Generating male-specific evidence also remains challenging: only four interventional trials specifically dedicated to male breast cancer were identified. One of them, SWOG S0511, was even terminated early because of poor accrual.

Toward truly evidence-based care?

Recommendations derived from female breast cancer remain essential and, in many cases, the available evidence supports their application to men. However, this approach reaches its limits when nearly all new therapies enter clinical practice without sufficient prospective data in male patients.

More immediate challenges also remain, including diagnostic delays, underuse of some recommended treatments, poor adherence to endocrine therapy, and competing mortality related to age and comorbidities. Together, these factors may contribute to the poorer outcomes observed in men.

The goal is therefore probably not to build an entirely separate approach to male breast cancer, but rather to generate enough evidence to determine precisely what can be extrapolated—and what should not be. This will require more systematic inclusion of men in breast cancer trials, sex-stratified analyses, and more rigorous use of real-world evidence.

About the author – Ana Espino
PhD in Immunology, specialized in Virology  
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions.