Hereditary breast and/or ovarian cancer syndrome

Hereditary breast and/or ovarian cancer syndrome (HBOC), also known as hereditary breast-ovarian cancer syndrome, is a genetic condition that significantly increases an individual's lifetime risk of developing breast cancer and ovarian cancer, as well as other cancers. It is most commonly caused by pathogenic variants (mutations) in the BRCA1 or BRCA2 tumor suppressor genes. Women carrying a BRCA1 mutation have an estimated 60–80% lifetime risk of breast cancer and a 40–60% risk of ovarian cancer, while BRCA2 mutation carriers have a 45–85% lifetime risk of breast cancer and a 10–30% risk of ovarian cancer. Men with BRCA2 mutations also have an elevated risk of breast cancer (approximately 6–8% lifetime risk) and prostate cancer. Both genes are also associated with increased risks of pancreatic cancer, and BRCA2 with melanoma. The syndrome primarily affects the breast and reproductive organs, but its cancer predisposition can extend to other body systems including the prostate, pancreas, and skin. Breast cancers in BRCA1 carriers are frequently triple-negative (estrogen receptor–negative, progesterone receptor–negative, and HER2-negative), which can influence treatment decisions. Ovarian cancers associated with HBOC often present as high-grade serous carcinomas and may be diagnosed at advanced stages due to the lack of effective early screening methods. Management of HBOC involves a combination of enhanced surveillance, risk-reducing strategies, and targeted therapies. Surveillance includes annual breast MRI and mammography starting at age 25–30, and consideration of transvaginal ultrasound and CA-125 monitoring for ovarian cancer, though the latter has limited sensitivity. Risk-reducing bilateral mastectomy can decrease breast cancer risk by approximately 90%, and risk-reducing bilateral salpingo-oophorectomy is recommended typically between ages 35–45 depending on the gene involved, substantially reducing ovarian and fallopian tube cancer risk. For individuals who develop cancer, PARP inhibitors (such as olaparib, rucaparib, and niraparib) have demonstrated significant efficacy in treating BRCA-associated breast and ovarian cancers by exploiting the defective DNA repair pathways in tumor cells. Platinum-based chemotherapy is also particularly effective in BRCA-related cancers. Genetic counseling and cascade testing of at-risk family members are essential components of care.

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