The lifetime risk for breast cancer in
men is 1 in 833 compared with 1 in 10 for a woman. Of affected men, 20% have a first-
degree family history of cancer; 4–14% of cases in males are attributed to germline
BRCA2 mutations and there is a 60–76% chance of a BRCA2 mutation in families with at
least one affected male. Klinefelter syndrome engenders a relative risk of 30–50 for
male breast cancer (owing to elevated circulating oestrogens); 5% of men with breast
cancers have this syndrome.
Other risk factors for breast cancer development in men
include elevated oestrogens (imbalance of oestrogen and testosterone), liver cirrhosis,
prostate cancer, age, obesity and smoking. In individuals who undergo male-to-female gender reassignment, hormonal stimulation may promote breast cancer development.
Clinically, men with breast cancer present at older age (60–70 years)
and with higher stage than women with breast cancer. Invasive ductal carcinoma is the most frequent subtype, whereas invasive lobular carcinoma is extremely
rare compared with female breast cancer; papillary carcinoma is the second most
frequent histological type.
In terms of the intrinsic subtypes, >90% of male
breast cancers are luminal A or luminal B; human epidermal growth factor receptor 2
(HER2)-positive and triple-negative breast cancer are extremely rare in men. AR is
often overexpressed in male breast cancer. Expression pathways of luminal genes
are also predominant; activation of fibroblast growth factor receptor 2 (FGFR2) and
phosphatidylinositol 3-kinase (PI3KCA) pathways are potential therapeutic targets to
be explored in the future. Prognosis is similar to stage-matched women with breast
cancer, although overall survival is worse because male patients with breast cancer are
often older, have more comorbidities and have lower life expectancy. Treatments
are largely extrapolated from female breast cancer, due to a paucity of available data.
As the vast majority of breast cancers in men are luminal cancers, the most important
therapy is endocrine therapy. In the adjuvant setting, tamoxifen (which binds to
and inhibits the ER) is the standard of care and aromatase inhibitors should not be used
alone (as these are associated with worse survival). In cases of absolute contra-indication for tamoxifen use, a combination of an aromatase inhibitor and a luteinizing
hormone-releasing hormone agonist can be considered, although this approach is
associated with higher toxicity. Recommendations for adjuvant chemotherapy
and radiation therapy are similar to those in women with luminal early breast cancer,
as are recommendations for management of advanced breast cancer.