Recommendations for Relatives with Family History of Ovarian Cancer
For relatives of patients with ovarian cancer, the priority is genetic counseling and risk assessment—not routine screening—as screening does not reduce mortality and causes significant harm through false-positive results and unnecessary surgeries. 1, 2
Do Not Perform Routine Ovarian Cancer Screening
Screening with CA-125 and transvaginal ultrasound is explicitly not recommended (Grade D) even for women with a family history of ovarian cancer, as the PLCO trial of 78,216 women (17% with family history) showed no mortality benefit, with 118 versus 100 deaths in the screened group (RR 1.18). 1, 2
Approximately 10% of screened women receive false-positive results with a positive predictive value of only 1-2%, leading to a 20:1 ratio of surgeries to screen-detected cancers. 2
Nearly 21 major complications occur per 100 surgical procedures performed for false-positive results, and one-third of women with false-positives undergo unnecessary oophorectomy. 2
Refer for Genetic Counseling Based on Specific Criteria
The critical first step is determining whether the relative meets criteria for genetic counseling referral:
Standard Referral Criteria 1, 3
Two or more first- or second-degree relatives with ovarian cancer or a combination of breast and ovarian cancer on the same side of the family
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
Additional NCCN Testing Criteria 1
Any first- or second-degree blood relative with epithelial ovarian/fallopian tube/primary peritoneal cancer at any age
Family member with breast cancer diagnosed ≤45 years, or ≤50 years with another close relative with breast cancer ≤50 years
Male relative with breast cancer
Genetic Testing Strategy
If genetic testing is pursued, test the affected family member first (the person who had ovarian cancer), not the unaffected relative. 3
Testing should ideally be performed on the affected family member who has the highest likelihood of carrying a mutation. 3
If the affected relative tests positive for a BRCA1/BRCA2 mutation, then the unaffected relative can undergo targeted testing for that specific familial mutation. 3
For Ashkenazi Jewish individuals, test for the three common founder mutations first; if negative and other criteria are met, consider full sequence testing. 1
If all affected family members are deceased, consider testing paraffin-derived DNA from deceased relatives if obtainable. 1
Management Based on Genetic Testing Results
If BRCA1/BRCA2 Mutation Identified 1, 3
Risk-reducing salpingo-oophorectomy (RRSO) is the definitive intervention:
Recommend RRSO ideally between ages 35-40 for BRCA1 carriers (or 40-45 for BRCA2 carriers) after completion of childbearing, individualized based on earliest age of ovarian cancer onset in the family. 1, 3
BRCA1 carriers have a 63% lifetime risk of ovarian cancer; BRCA2 carriers have a 27% lifetime risk. 4
Counseling must include discussion of reproductive desires, extent of cancer risk, degree of protection, management of menopausal symptoms, and possible short-term hormone replacement therapy. 1
For women who decline RRSO:
Consider transvaginal ultrasound plus CA-125 every 6 months starting at age 35 years (or 5-10 years earlier than earliest family diagnosis), preferably on days 1-10 of menstrual cycle for premenopausal women. 1
Note this surveillance has not been proven to reduce mortality but may be offered as an alternative to RRSO. 1
Additional surveillance for BRCA carriers:
Breast self-exam training and monthly BSE starting at age 18 years 1
Clinical breast exam semiannually starting at age 25 years 1
Annual mammogram and breast MRI screening starting at age 25 years or individualized based on earliest age of onset in family 1, 3
Discuss risk-reducing mastectomy on a case-by-case basis 1
If No Mutation Identified or Testing Not Pursued
Focus on symptom awareness education rather than screening tests, as early-stage ovarian cancer is usually asymptomatic. 2
Educate about risk-reducing factors: oral contraceptive use reduces ovarian cancer risk by approximately 50%, and other protective factors include pregnancy, breastfeeding, and bilateral tubal ligation. 2, 4, 5
Advise about possible inherited cancer risk to other relatives and recommend they also consider genetic counseling. 1
Critical Pitfalls to Avoid
Do not order CA-125 or transvaginal ultrasound as "screening" for asymptomatic relatives—this causes more harm than benefit even in high-risk women. 1, 2
Do not test the unaffected relative first—always attempt to test an affected family member to identify the specific familial mutation. 3
Do not assume family history alone predicts mutation status—among ovarian cancer patients with BRCA mutations, 35-37% had no family history of breast or ovarian cancer. 6
Do not dismiss limited family structures—women with fewer than two first- or second-degree female relatives may have underestimated probability of familial mutation. 1