From genetic testing to prevention: an integrated clinical pathway for hereditary risk assessment in tubo-ovarian cancer.

Abstract

Hereditary tubo-ovarian cancer risk assessment has evolved from a BRCA1/2-centered consultation to an integrated prevention pathway that begins at diagnosis and extends to unaffected relatives. Germline testing is now justified for patients with epithelial tubo-ovarian cancer because actionable pathogenic variants are common enough that family-history-only referral misses many carriers. The central clinical challenge is no longer whether testing matters, but whether testing is interpreted and implemented in a way that prevents cancer. BRCA1 and BRCA2 remain the highest-impact tubo-ovarian cancer predisposition genes, but Lynch syndrome genes, BRIP1, RAD51C, RAD51D, PALB2, and selected rare histology-directed syndromes require distinct counseling. Gene-specific penetrance, age-specific risk, family history, comorbidities, reproductive plans, and menopause consequences should shape the timing of risk-reducing surgery. Tumor testing improves therapeutic selection and can identify possible hereditary variants, but tumor-only testing does not replace germline testing when hereditary evaluation is indicated. Cascade testing should be measured and resourced as part of tubo-ovarian cancer care rather than treated as a passive family responsibility. Mainstream testing, traceback programs, and navigation-supported cascade testing offer pragmatic implementation models, but access gaps remain. For gynecologic oncology clinicians, modern hereditary risk assessment should be understood as a multi-disciplinary prevention intervention: testing is the entry point, not the endpoint. This narrative review synthesizes gene-specific counseling, tumor-germline interpretation, and implementation strategies into a clinically oriented pathway from diagnosis to prevention for patients and relatives.