Breast cancer in men

Breast cancer in men, The male breast is a rudimentary organ that is limited to ducts in the retro-aerolar area, expressing oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). Benign and malignant lesions presenting as retro-aerolar lumps can occur, although male breast cancer is rare: less than 1% of all breast cancers occur in men and less than 0.5% of deaths in men can be attributed to breast cancer.

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.