A 38-year-old woman presents to the genetics clinic with a personal history of triple-negative breast cancer diagnosed at age 35 and a family history of ovarian cancer in her mother at age 42. Genetic testing confirms a pathogenic mutation in BRCA1. The pedigree pattern shown in the diagram is labeled **B** (Hereditary breast-ovarian cancer). Which of the following management strategies is MOST appropriate to reduce her ovarian cancer risk in this BRCA1 carrier?

Question

Accepted Answer

D. Bilateral salpingo-oophorectomy by age 35–40 years. ## Why Bilateral salpingo-oophorectomy by age 35–40 years is right

According to NCCN guidelines and the clinical anchor, BRCA1 carriers have a 39–44% lifetime ovarian cancer risk and should undergo bilateral salpingo-oophorectomy (BSO) by age 35–40 years, which reduces ovarian cancer risk by approximately 80% and also reduces breast cancer risk by ~50%. This is the gold-standard risk-reducing surgical intervention for BRCA1 carriers, as ovarian cancer screening (ultrasound and CA-125) has not been shown to improve survival in this high-risk population. The patient is already 38 years old and should be counseled for urgent BSO.

## Why each distractor is wrong

- **Annual transvaginal ultrasound and CA-125 screening indefinitely**: While screening may detect some ovarian cancers, it does not reduce mortality in BRCA carriers and is NOT recommended as a primary management strategy. NCCN guidelines emphasize risk-reducing surgery over surveillance for ovarian cancer in BRCA1 carriers.
- **Tamoxifen chemoprevention starting at age 40**: Tamoxifen and aromatase inhibitors are chemoprevention options primarily for BRCA2 carriers with hormone-receptor-positive breast cancer risk. They do not reduce ovarian cancer risk and are not first-line for BRCA1 carriers, who typically develop triple-negative (hormone-receptor-negative) tumors.
- **Prophylactic bilateral mastectomy alone without oophorectomy**: While prophylactic mastectomy reduces breast cancer risk by ~90%, it does NOT address ovarian cancer risk. BRCA1 carriers require BOTH breast surveillance/prophylaxis AND oophorectomy to manage their dual cancer risks comprehensively.

**High-Yield:** BRCA1 carriers require bilateral salpingo-oophorectomy by age 35–40; BRCA2 carriers by age 40–45. This single intervention reduces both ovarian and breast cancer risk.

[cite: NCCN Genetic/Familial High-Risk Assessment Breast/Ovarian 2024; clinical anchor on BRCA1/BRCA2 penetrance, ovarian cancer risk, and BSO timing]

Answer

A. Annual transvaginal ultrasound and CA-125 screening indefinitely

Answer

B. Prophylactic bilateral mastectomy alone without oophorectomy

Answer

C. Tamoxifen chemoprevention starting at age 40

Explanation

Why Bilateral salpingo-oophorectomy by age 35–40 years is right

Why each distractor is wrong

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