Male Breast Cancer: Epidemiology, Diagnosis, Molecular Mechanisms, Therapeutics, and Future Prospective
Abstract
Male breast cancer (MBC) is rare, representing 0.5%-1% of all breast cancers, but its incidence is increasing due to improved diagnostics and awareness. MBC typically presents in older men, is human epidermal growth factor receptor 2 (HER2)-negative and estrogen receptor (ER)-positive, and lacks routine screening, leading to delayed diagnosis and advanced disease. Major risk factors include hormonal imbalance, radiation exposure, obesity, alcohol use, and Breast Cancer Gene 1 and 2 (BRCA1/2) mutations. Clinically, it may resemble gynecomastia but usually appears as a unilateral, painless mass or nipple discharge. Advances in imaging and liquid biopsy have enhanced early detection. Molecular mechanisms involve hormonal signaling, HER2/epidermal growth factor receptor (EGFR) pathways, tumor suppressor gene alterations, and epigenetic changes. While standard treatments mirror those for female breast cancer, emerging options such as cyclin-dependent kinase 4 and 6 (CDK4/6), and poly(ADP-ribose) polymerase (PARP) inhibitors, immunotherapy, and precision medicine are reshaping management. Incorporating artificial intelligence, molecular profiling, and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.