What is the most appropriate next step in managing a 55-year-old postmenopausal woman with a family history of ovarian cancer who is currently asymptomatic and has no known genetic testing for BRCA1 (Breast Cancer Gene 1) and BRCA2 (Breast Cancer Gene 2) mutations?

Management of Asymptomatic Postmenopausal Woman with Family History of Ovarian Cancer

The most appropriate next step is genetic counseling and risk assessment to determine eligibility for BRCA1/BRCA2 genetic testing, not routine screening with CA-125 or pelvic ultrasound. 1

Rationale Against Routine Screening

The USPSTF explicitly recommends against screening asymptomatic women without known genetic mutations for ovarian cancer using transvaginal ultrasound or CA-125 testing (Grade D recommendation). 1 This applies even to women with a family history of ovarian cancer, as screening does not decrease ovarian cancer mortality and leads to important harms, including unnecessary major surgical interventions in women who do not have cancer. 1

Annual screening with transvaginal ultrasonography and serum CA-125 testing in women does not decrease ovarian cancer mortality, and the harms of screening outweigh any potential benefits. 1

The Correct Approach: Genetic Risk Assessment

Step 1: Determine if She Meets Criteria for Genetic Counseling

Women with a family history of ovarian cancer should be considered for genetic counseling to evaluate their potential risks. 1 Specifically, "increased-risk family history" generally means:

• Two or more first- or second-degree relatives with a history of ovarian cancer or a combination of breast and ovarian cancer 1
• For women of Ashkenazi Jewish descent: a first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer 1

Step 2: Genetic Counseling and Testing Considerations

If she meets criteria based on family history assessment, she should receive genetic counseling with discussion of BRCA1/BRCA2 testing. 1, 2 The National Comprehensive Cancer Network recommends genetic testing for individuals with a first- or second-degree blood relative meeting specific criteria, including family members with epithelial ovarian/fallopian tube/primary peritoneal cancer. 2, 3

Key point: Approximately 10% of ovarian cancers occur in association with BRCA1/BRCA2 mutations, and BRCA1 and BRCA2 are responsible for half of all families containing two or more ovarian cancer cases. 4, 5

Step 3: Importance of Testing the Affected Family Member First

Initial genetic testing should ideally be performed on an affected family member (the relative with ovarian cancer) who has the highest likelihood of carrying a mutation. 1, 2, 3 If the affected relative tests positive for a mutation, then this patient can undergo targeted testing for that specific familial mutation. 1

If no affected family member is available for testing, testing of unaffected individuals should be considered, though significant limitations of interpreting test results must be discussed. 1

What About Symptom Counseling?

While counseling about ovarian cancer symptoms is reasonable and should be part of routine care, it is not a substitute for proper genetic risk assessment in a woman with a family history. 1 Symptom awareness is important but does not address her underlying hereditary risk, which could be as high as 40-60% lifetime risk for ovarian cancer if she carries a BRCA mutation. 4

Common Pitfalls to Avoid

• Do not order CA-125 or pelvic ultrasound for screening in asymptomatic women, even with family history, as this leads to false positives and unnecessary surgeries without mortality benefit. 1
• Do not skip genetic counseling before ordering genetic testing, as informed consent and proper interpretation of results (including variants of uncertain significance) require expert guidance. 1
• Do not assume a negative family history rules out hereditary risk - more than half of patients with BRCA1 mutations have family histories that would be considered unremarkable. 5
• Do not test the unaffected patient first if an affected relative is available, as this reduces the informativeness of testing. 1, 2

If She Tests Positive for a BRCA Mutation

If genetic testing identifies a deleterious BRCA1/BRCA2 mutation, she should be offered:

• Enhanced surveillance with breast MRI and mammography starting at age 25-30 1
• Risk-reducing salpingo-oophorectomy (RRSO), typically recommended between ages 35-40 after childbearing is complete for BRCA1 carriers, and ages 40-45 for BRCA2 carriers 1, 6
• Consideration of risk-reducing mastectomy 1

RRSO reduces ovarian cancer risk by approximately 80-90% and also reduces breast cancer risk. 6