Sex Differences in Breast Cancer: Implications for Immunotherapy and Combination Treatments

Background: Sex differences in breast cancer are critical determinants of tumor biology, treatment responses, and clinical outcomes. Despite breast cancer’s predominance in women, men are also affected, with distinct biological and clinical characteristics. However, research on sex-specific influences in breast cancer remains limited, particularly regarding immunotherapy and combination treatments. Objectives: This study explores the molecular, genetic, and immune-related mechanisms underlying sex differences in breast cancer. It evaluates the implications for immunotherapy and combination treatments and emphasizes the need for personalized, sex-specific therapeutic approaches. Methods: A comprehensive review of current literature was conducted to examine sex differences in breast cancer, focusing on hormonal, genetic, and immunological mechanisms. Research on immune response variations and clinical trial data related to breast cancer treatment outcomes was analyzed. Evidence from studies on immunotherapy and combination treatment strategies was reviewed to identify sex-specific outcomes, therapeutic challenges, and potential personalized treatment approaches. Results: Sex hormones, chromosomal differences, and immune system variations significantly influence tumor behavior and therapeutic responses. Men and women exhibit different outcomes with immune checkpoint inhibitors, with variations in efficacy and adverse effects. Combination treatments involving immunotherapy and hormonal or chemotherapy-based approaches show potential but require sex-specific considerations. Conclusions: Sex differences must be recognized as a critical determinant in breast cancer treatment. Integrating sex as a biological variable in clinical trials and developing sex-specific biomarkers can enhance personalized medicine. 1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). 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