Hereditary cancer syndromes with gynecological cancer risk: focus on prevention strategies.

BACKGROUND

Hereditary cancer syndromes, including pathogenic variants in BRCA1/2 and mismatch-repair genes, confer a substantial risk of several malignancies, including ovarian, endometrial, and fallopian tube cancers. Given the limited efficacy of current screening strategies, particularly for ovarian cancer, a prevention-focused approach is required. This review synthesizes evidence on identification, risk stratification, surveillance, chemoprevention, and prophylactic surgery in women with inherited gynecologic cancer susceptibility, proposing a precision-prevention framework.

METHODS

A structured search of MEDLINE, Embase, and the Cochrane Library was conducted through July 2025. Original studies, reviews, and guidelines in English were included following independent screening and full-text assessment by two authors.

RESULTS

Expanded germline testing, universal mismatch-repair screening, and genomic profiling have improved carrier identification beyond family history-based criteria. Integrated counseling models enhance informed decision-making and access to care. Conventional surveillance tools show limited sensitivity; emerging strategies, including circulating tumor DNA assays and artificial intelligence, require further validation. Hormonal and anti-inflammatory agents demonstrate potential for risk reduction. Prophylactic surgery, including salpingo-oophorectomy, hysterectomy, or investigational salpingectomy with delayed oophorectomy, remains central, requiring multidisciplinary evaluation and attention to fertility, menopausal health, and patient preferences. Ethical and health-economic considerations remain critical in clinical practice and policy development. Further studies are warranted to better elucidate the potential role of liquid biopsy, microbiota, and targeted vaccination strategies.

CONCLUSIONS

Prevention of gynecologic cancers in genetically predisposed women requires an integrated strategy that includes comprehensive genetic assessment, risk-adapted surveillance, evidence-based risk-reduction interventions, and multidisciplinary coordination. Implementing and refining precision prevention frameworks is crucial to optimize outcomes and translate genetic risk into tailored preventive care.