Contemporary risk assessment and risk-reducing strategies for tubo-ovarian cancer in women with BRCA pathogenic variants
Abstract
Tubo-ovarian cancer represents the most lethal gynecologic malignancy, and its burden is compounded by the absence of effective screening and the substantial lifetime risk carried by women with germline BRCA1 or BRCA2 pathogenic variants. While risk-reducing salpingo-oophorectomy remains the standard for prevention, conferring reduction in tubo-ovarian cancer risk and improved overall survival, it also induces premature menopause with significant effects on quality of life and bone, cardiovascular, and sexual health. These consequences have driven the exploration of alternative preventive strategies, and a paradigm shift toward individualized risk assessment. Emerging data highlight that tubo-ovarian cancer risk among BRCA pathogenic variant carriers is not uniform but influenced by gene type, variant position, family history, and modifiable factors such as parity, breastfeeding, and oral contraceptive use. Modern risk models integrate genetic, familial, and lifestyle data to refine personalized estimates and guide the timing of intervention. Concurrently, the understanding that many high-grade serous carcinomas originate in the fallopian tube has prompted evaluation of risk-reducing salpingectomy with delayed oophorectomy as a staged surgical strategy that may balance oncologic safety with preservation of hormonal function. Ultimately, management of BRCA pathogenic variant carriers must combine genomic precision, reproductive planning, and patient-centered counseling to…
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