Prophylactic Mastectomy in Patients with Specific HLA Gene Variants: Benefits and Controversies

• DOI: https://doi.org/10.22533/at.ed.1595925300111

• Palavras-chave: Prophylactic mastectomy; HLA gene polymorphisms; Breast cancer risk assessment; Genetic counseling; Immune surveillance.

• Keywords: Prophylactic mastectomy; HLA gene polymorphisms; Breast cancer risk assessment; Genetic counseling; Immune surveillance.

• Abstract: INTRODUCTION Prophylactic mastectomy is an established preventive strategy for individuals carrying BRCA mutations, yet its role in patients with specific HLA gene variants remains uncertain. While some HLA polymorphisms have been associated with increased breast cancer susceptibility, others appear to confer protection. The immunological mechanisms involved in tumor surveillance and immune evasion suggest that HLA variants may contribute to breast cancer risk, but their clinical significance in surgical prevention has not been fully determined. Current risk stratification models do not routinely incorporate HLA genotyping, leading to uncertainty in decision-making regarding prophylactic surgery in this subgroup.  OBJETIVE To evaluate the necessity, effectiveness, and clinical rationale for prophylactic mastectomy in patients with specific HLA gene variants, considering genetic predisposition, immunological mechanisms, and surgical outcomes.  METHODS This is a narrative review which included studies in the MEDLINE – PubMed (National Library of Medicine, National Institutes of Health), COCHRANE, EMBASE and Google Scholar databases, using as descriptors: “Prophylactic mastectomy” AND “HLA gene polymorphisms” OR “Breast cancer risk assessment” OR “Genetic counseling” OR “Immune surveillance” in the last  years. RESULTS AND DISCUSSION The results highlight the lack of definitive evidence supporting prophylactic mastectomy in HLA-positive individuals. Unlike BRCA carriers, for whom mastectomy significantly reduces cancer incidence, the variable risk associated with HLA variants complicates surgical recommendations. Psychological distress and decisional conflict are common among patients faced with uncertain genetic risk, and disparities in access to genetic counseling further exacerbate these challenges. Breast reconstruction options and postoperative quality of life were also analyzed, with findings indicating that while many patients report satisfaction, others experience regret, particularly when risk estimates are ambiguous.  CONCLUSION Given the current gaps in evidence, prophylactic mastectomy in HLA-positive patients should be approached with caution. Future research should prioritize large-scale studies to determine the true oncogenic impact of HLA polymorphisms and assess whether surgical intervention provides a survival benefit. Until more conclusive data are available, risk reduction strategies should focus on individualized counseling, enhanced surveillance, and potential non-surgical interventions tailored to the specific genetic profile of each patient.