What is the most appropriate initial step in managing a postmenopausal woman with a family history of ovarian cancer who is asymptomatic and has no known genetic testing?

Management of Asymptomatic Postmenopausal Woman with Family History of Ovarian Cancer

The most appropriate initial step is C: No need for screening test until the patient becomes symptomatic—instead, refer for genetic counseling and risk assessment based on detailed family history. 1, 2

Why Screening Tests Are Not Recommended

The USPSTF gives a Grade D recommendation (harms outweigh benefits) against screening for ovarian cancer in asymptomatic women, even those with a family history. 3, 1 This recommendation is based on:

• The PLCO trial of 78,216 women (17% with family history of breast or ovarian cancer) showed no reduction in ovarian cancer deaths with annual CA-125 and transvaginal ultrasound screening (118 vs 100 deaths; relative risk 1.18, CI 0.82-1.71). 3
• No significant shift in stage at diagnosis occurred despite screening, indicating that earlier detection did not translate to improved outcomes. 3
• Approximately 10% of screened women receive false-positive results, with a positive predictive value of only 1-2%. 1
• One-third of women with false-positive results undergo unnecessary oophorectomy, resulting in a 20:1 ratio of surgeries to screen-detected cancers. 1
• Nearly 21 major complications occur per 100 surgical procedures performed for false-positive results. 1

The Correct Initial Step: Genetic Risk Assessment

Women with a family history of ovarian cancer should be evaluated for genetic counseling referral based on specific family history criteria. 3, 2 The key is to determine whether she meets criteria for genetic counseling:

Referral Criteria for Genetic Counseling:

• Two or more first- or second-degree relatives with ovarian cancer 1, 2
• A combination of breast and ovarian cancer in the family 1, 2
• For Ashkenazi Jewish women: one first-degree relative or two second-degree relatives on the same side of the family with breast or ovarian cancer 1
• Any first- or second-degree blood relative with epithelial ovarian/fallopian tube/primary peritoneal cancer 2

Why Genetic Counseling Comes First:

• Approximately 10% of ovarian cancers occur in association with BRCA1/BRCA2 mutations. 2
• Women with BRCA1 mutations have a cumulative ovarian cancer risk of 56% by age 70. 1
• If genetic testing identifies a deleterious BRCA mutation, management changes entirely—including consideration of risk-reducing bilateral salpingo-oophorectomy, which reduces ovarian cancer risk by 69-100% and all-cause mortality by 55%. 3, 2
• Initial genetic testing should ideally be performed on an affected family member first, as this has the highest likelihood of identifying a mutation. 2

Management Based on Genetic Testing Results

If BRCA Mutation Identified:

• Risk-reducing salpingo-oophorectomy typically recommended between ages 35-40 after childbearing is complete for BRCA1 carriers, and ages 40-45 for BRCA2 carriers. 2
• Enhanced breast surveillance with MRI and mammography starting at age 25-30. 2
• This is the only scenario where management differs from average-risk women. 3

If No BRCA Mutation or Testing Not Indicated:

• Focus on symptom awareness rather than screening tests. 1
• Educate about ovarian cancer symptoms (though early-stage disease is usually asymptomatic). 1, 4
• Discuss risk-reducing factors: oral contraceptive use reduces ovarian cancer risk by approximately 50%, as do pregnancy, breastfeeding, and bilateral tubal ligation. 3, 1, 4

Important Caveats

• The USPSTF recommendation against screening applies even to women with family history, unless they have known BRCA mutations. 3
• Only 5-10% of ovarian cancer patients have a significant family history, but identifying these high-risk individuals is critical. 1
• The UK Familial Ovarian Cancer Screening Study showed different results for women with ≥10% lifetime risk based on family history or known genetic mutation (sensitivity 81.3-87.5%, PPV 25.5%), suggesting screening may be considered only for confirmed BRCA mutation carriers or very strong family history. 1
• Primary care providers should periodically reassess family history (comprehensive review at least every 5-10 years), as family history can change over time. 3