Ovarian Cancer Risk Management in Individuals with Strong Family History
Women with a strong family history of ovarian cancer should be referred for genetic counseling and testing, followed by risk-reducing salpingo-oophorectomy (RRSO) if a BRCA mutation is identified—not screening, as ovarian cancer screening does not reduce mortality and causes significant harm through false-positive results and unnecessary surgeries. 1, 2
Genetic Counseling and Testing Strategy
Who Qualifies for Genetic Counseling
Women meeting any of these criteria require genetic counseling referral 1, 2, 3:
- Two or more first- or second-degree relatives with ovarian cancer or a combination of breast and ovarian cancer 1, 2
- Ashkenazi Jewish descent with one first-degree relative (or two second-degree relatives on the same side) with breast or ovarian cancer 1, 2
- Any first-degree relative (mother, sister, daughter) with ovarian, fallopian tube, or primary peritoneal cancer—this alone is sufficient regardless of additional family history 2
Optimal Testing Approach
Test the affected family member first (the relative with ovarian cancer) as they have the highest probability of carrying a mutation 2. If that relative tests positive, the patient can then undergo targeted single-site testing for the specific familial mutation, which is faster and less expensive 2. All women with epithelial ovarian cancer should undergo germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes 1.
Multigene Panel Testing
Current guidelines recommend multigene panel testing of clinically validated HBOC (Hereditary Breast-Ovarian Cancer) genes rather than BRCA1/2 alone 1. Approximately 25% of ovarian cancers are caused by heritable genetic conditions, with BRCA1/2 accounting for 40% of familial cases and other genes (including Fanconi anemia pathway genes) accounting for an additional 6% of all ovarian cancers 1, 4.
Evidence-Based Risk Reduction Strategies
Risk-Reducing Salpingo-Oophorectomy (Primary Strategy)
RRSO is the only evidence-based intervention that reduces ovarian cancer mortality in BRCA mutation carriers 2, 5, 4:
- BRCA1 carriers: Perform RRSO between ages 35-40 (after childbearing is complete) 2, 5
- BRCA2 carriers: Perform RRSO between ages 40-45 2, 5
- This intervention dramatically reduces ovarian cancer mortality when performed at these ages 2
Risk-Reducing Medications
Oral contraceptives reduce ovarian cancer risk by approximately 50% and represent an important non-surgical option 1, 5, 3. Other protective factors include pregnancy, breastfeeding, and bilateral tubal ligation 1, 5, 3.
Enhanced Breast Cancer Surveillance for BRCA Carriers
BRCA mutation carriers require annual MRI and mammography beginning at age 25-30, which improves early detection and survival 2. After ovarian cancer diagnosis in BRCA carriers, breast cancer surveillance remains important for those achieving sustained remission beyond 2 years, as breast cancer risk becomes comparable to or exceeds ovarian cancer recurrence risk 6.
Critical Pitfall: Screening Does NOT Work
The USPSTF gives a Grade D recommendation (recommends against) ovarian cancer screening in ALL women, including those with family history 1, 2, 5, 3. This strong recommendation is based on definitive evidence:
Why Screening Fails
- The PLCO trial of 78,216 women (17% with family history) showed no reduction in ovarian cancer deaths with annual CA-125 and transvaginal ultrasound—118 deaths in the screened group versus 100 in controls (RR 1.18) 1, 5
- Screening outcomes were not separately reported for the family history subgroup, but the overall trial showed no benefit 1
- No shift in stage distribution occurred with screening 5
Harms of Screening
- 10% false-positive rate: Approximately 300-350 women without cancer are recalled per 10,000 screened annually 5, 3
- Positive predictive value of only 1-2%: Only 2% of positive screening tests represent actual cancer 5, 3
- 20:1 surgery-to-cancer ratio: One-third of women with false-positives undergo oophorectomy, resulting in 20 surgeries for every screen-detected cancer 2, 5
- Major complications: Nearly 21 major complications occur per 100 surgical procedures performed for false-positive results 5
Exception for Confirmed High-Risk Mutation Carriers
The UK Familial Ovarian Cancer Screening Study showed different results for women with ≥10% lifetime risk based on confirmed genetic mutations, with sensitivity of 81.3-87.5% and PPV of 25.5% 5. Screening may be considered for women with confirmed BRCA mutations using transvaginal ultrasound and CA-125 with the ROCA algorithm, though RRSO remains the definitive risk-reduction strategy 5.
Pre-Test Counseling Requirements
Genetic counseling must address 1, 2:
- Probability of finding a mutation based on family history and ethnicity
- Medical implications including impact on current cancer treatment and future cancer prevention
- Psychological implications for the individual and family members
- Meaning of possible results including variants of uncertain significance (VUS)
- How results will influence medical management including enhanced surveillance and risk-reducing surgeries
- Familial implications indicating which relatives need testing
- Reproductive options including pregestational testing (PGT)
Clinical decision making should never be based on a variant of uncertain significance 1.
Multidisciplinary Follow-Up
Risk management is a lifelong endeavor best undertaken in specialized high-risk clinics that include 1:
- Imaging services
- Gynecologists and breast/plastic surgeons
- Genetic counselors
- Psychologists for bio-psychosocial support
- Linked oncologists
These clinics provide clinical expertise, continuity of care, consistency in recommendations, and access to clinical trials 1.
Cascade Testing for Family Members
First- or second-degree blood relatives of a patient with ovarian cancer who has a known germline pathogenic variant should be offered individualized genetic risk evaluation, counseling, and genetic testing 1, 2. Enhancing awareness and availability of testing in at-risk relatives should be a priority 1. Strategies that improve familial testing, including allowing direct communication by the medical team, should be sought 1.
Clinical Vigilance Instead of Screening
For women with family history who do not have confirmed mutations, focus on symptom awareness rather than screening 5, 3:
- Abdominal or pelvic pain
- Unexplained weight loss
- Bloating or increased abdominal size
- Early satiety
Early-stage ovarian cancer is usually asymptomatic, making symptom-based detection challenging 5.