Special considerations in the evaluation and management of breast cancer in men1

Breast cancer in men is relatively uncommon but its incidence has been rising. Traditionally, the management of breast cancer in men is based on extrapolation from clinical trials of breast cancer in women, due to the much more extensive data available in women with this disease. There are, however, unique characteristics that distinguish breast cancer in men and these should be taken into consideration when managing this patient population. Breast cancer in men is more frequently estrogen receptor (ER) and progesterone receptor (PgR) positive, and less frequently HER2 amplified. Lobular carcinoma, which accounts for 10-15% of breast cancers in women, is exceptionally rare in men. Genetic risk factors, particularly BRCA2 mutations, are increasingly recognized as a key risk factor for breast cancer in men and genetic testing is now routinely recommended for all men diagnosed with breast cancer. Tamoxifen remains the gold standard endocrine therapy for breast cancer in men, but other endocrine agents such as the aromatase inhibitors (AI) and fulvestrant are increasingly being used. While superior to tamoxifen in postmenopausal women, the use of AIs for adjuvant therapy in men with breast cancer may not be optimal since the physiology of hormonal regulation in men resembles that of premenopausal rather than postmenopausal women. Emerging areas of investigation include the role of genomic risk stratification to gain further insight into the biology of breast cancer in men, the study of the androgen receptor (AR) as a therapeutic target, and the role of gonadal suppression in the management of the disease. There is clearly a more consorted effort to study breast cancer in men as a unique disease in order to have a better understanding of its biology and we are likely to witness further advances that will help us better manage this unique disease situation.