What are the recommendations for a female patient with a personal or family history of breast cancer to reduce her risk of developing ovarian cancer?

Ovarian Cancer Risk Reduction in Women with Personal or Family History of Breast Cancer

Women with a personal history of breast cancer and a family history of breast or ovarian cancer should be referred for genetic counseling and BRCA testing, as identifying a BRCA mutation enables risk-reducing salpingo-oophorectomy (RRSO) which dramatically reduces ovarian cancer mortality. 1, 2

Immediate Action: Genetic Counseling Referral

Refer for genetic counseling if any of the following criteria are met:

• Personal history of breast cancer PLUS:

  • Two or more first- or second-degree relatives with ovarian cancer on the same side of the family 1
  • One first-degree relative with ovarian, fallopian tube, or primary peritoneal cancer at any age 1
  • Combination of breast and ovarian cancer in first- or second-degree relatives on the same side 1
  • Breast cancer diagnosis before age 40 with any family history of breast or ovarian cancer 3, 2

• For Ashkenazi Jewish women: One first-degree relative OR two second-degree relatives on the same side with breast or ovarian cancer 1, 2

• Any woman with epithelial ovarian, tubal, or peritoneal cancer should receive genetic counseling regardless of family history 1

Risk Stratification Based on BRCA Status

If BRCA1 Mutation Identified:

• Lifetime ovarian cancer risk: 37-62% 3
• Risk-reducing salpingo-oophorectomy recommended between ages 35-40 (after childbearing complete) 2
• This intervention dramatically reduces ovarian cancer mortality when performed in this age window 2

If BRCA2 Mutation Identified:

• Lifetime ovarian cancer risk: 11-23% 3
• Risk-reducing salpingo-oophorectomy recommended between ages 40-45 2

If No BRCA Mutation Found:

• Do NOT pursue ovarian cancer screening - the USPSTF gives a Grade D recommendation (harms outweigh benefits) against screening even in high-risk women 4, 2
• Focus on symptom awareness and risk-reducing factors 4

Risk-Reducing Strategies Beyond Surgery

Oral contraceptive use reduces ovarian cancer risk by approximately 50% 1, 4

Additional protective factors include:

• Pregnancy 1, 4
• Breastfeeding 1, 4
• Bilateral tubal ligation 1, 4

Critical Management Considerations for Women with Both Breast and Ovarian Cancer History

For BRCA carriers diagnosed with early-stage ovarian cancer:

• Continue breast cancer surveillance with annual MRI and mammography 3, 2
• Consider prophylactic mastectomy if sustained remission achieved (>2 years) 5
• After 2 years in remission, breast cancer risk becomes comparable to or exceeds ovarian cancer recurrence risk 5

For BRCA carriers with advanced ovarian cancer:

• If no remission achieved, breast cancer surveillance is not of value 5
• If sustained remission >2-5 years, initiate aggressive breast cancer screening and consider prophylactic mastectomy 5

Chemoprevention for Breast Cancer

Tamoxifen reduces contralateral breast cancer risk in BRCA carriers with existing breast cancer 3

However, tamoxifen has NOT been demonstrated to prevent primary breast cancer in BRCA mutation carriers 3

What NOT to Do: Avoid Ovarian Cancer Screening

Never order CA-125 or transvaginal ultrasound for ovarian cancer screening, even in high-risk women 4, 2

The evidence is clear:

• The PLCO trial of 78,216 women (17% with family history) showed NO reduction in ovarian cancer deaths with screening (118 vs 100 deaths, RR 1.18) 4
• Approximately 10% of screened women receive false-positive results 4, 2
• Positive predictive value is only 1-2% 4
• One-third of women with false-positives undergo unnecessary oophorectomy 4
• This creates a 20:1 ratio of surgeries to screen-detected cancers 4, 2
• Nearly 21 major complications occur per 100 surgical procedures for false-positive results 4

Risk-reducing surgery, not screening, is the evidence-based approach for BRCA mutation carriers 2

Optimal Testing Strategy

If a family member has ovarian cancer, test that affected relative first - they have the highest likelihood of carrying a mutation 2

If the affected relative tests positive, the patient can then undergo targeted testing for that specific familial mutation, which is faster and less expensive 2

Pre-test counseling must cover:

• Probability of finding a mutation 2
• Implications for patient and family members 2
• Meaning of possible results including variants of uncertain significance 2
• How results will influence medical management including enhanced surveillance and risk-reducing surgeries 2

Family Cascade Testing

Once a BRCA mutation is identified, cascade testing should be offered to all at-risk family members 2

Carriers should be encouraged to advise close family members to obtain genetic counseling 3