I am a woman whose mother had ovarian cancer and my test for BRCA1, BRCA2 and other high‑risk hereditary ovarian cancer genes is negative; should I consider prophylactic bilateral oophorectomy for risk reduction?

Prophylactic Oophorectomy in Women with Negative Genetic Testing but Maternal Ovarian Cancer History

No, prophylactic bilateral oophorectomy is not recommended for women with negative BRCA1/2 and other high-risk hereditary ovarian cancer gene testing, even with a maternal history of ovarian cancer, as the lifetime ovarian cancer risk remains close to the general population baseline.

Risk Stratification Without Identified Mutation

Your actual ovarian cancer risk is approximately 7.5% lifetime risk (if mother had ovarian cancer), compared to the general population baseline of 1.8%, representing a relative risk of 4.3 1. This is substantially lower than the 36-63% lifetime risk seen in confirmed BRCA1/2 mutation carriers 2.

• Women with one first-degree relative (mother) with ovarian cancer have a lifetime risk of 7.5%, which is approximately four times the general population risk but does not meet the threshold for prophylactic surgery 1.
• The threshold for considering prophylactic oophorectomy historically requires a lifetime risk of at least 5% or higher, but current guidelines reserve this intervention primarily for confirmed genetic mutation carriers 2.
• If your mother developed ovarian cancer before age 45, your lifetime risk may be as high as 25% (relative risk 14.2), which could warrant reconsideration of prophylactic surgery even without identified mutation 1.

Why Prophylactic Surgery Is Not Recommended in Your Case

Prophylactic bilateral salpingo-oophorectomy is specifically indicated for women with confirmed BRCA1/2 or other high-risk pathogenic variants (RAD51C, RAD51D, BRIP1, PALB2, Lynch syndrome genes), not for family history alone when genetic testing is negative 2, 3.

• The 2021 NCCN guidelines state that bilateral salpingo-oophorectomy should be performed in women with confirmed BRCA1/2 pathogenic or likely pathogenic variants after completion of childbearing 2.
• UK guidelines from 2023 specify that bilateral salpingo-oophorectomy is recommended for carriers of germline pathogenic variants in genes associated with ovarian cancer, requiring genetic confirmation 2.
• The 1998 French National Ad Hoc Committee explicitly stated that prophylactic oophorectomy should not be performed on women with a lifetime risk of less than 5% of ovarian cancer, calling such surgery "mutilation" when performed without medical indication 2.

Important Caveats About Negative Genetic Testing

Negative genetic testing does not completely eliminate hereditary risk, as 2-12% of high-risk families may harbor large genomic alterations not detected by standard sequencing, and there may be undiscovered mutations 2.

• If your family has three or more cases of ovarian cancer across first- and second-degree relatives, you may still be at higher risk despite negative testing, and repeat genetic counseling should be considered 1.
• The Breast Cancer Linkage Consortium defines hereditary ovarian cancer as families with three or more cases of ovarian cancer, or five or more breast/ovarian cancers combined 1.
• If your mother's ovarian cancer occurred before age 45, this suggests possible hereditary cancer even with current negative testing, and expanded genetic panel testing or future retesting may be warranted 1.

Recommended Management Strategy Instead

Enhanced surveillance is the appropriate strategy for women with family history but negative genetic testing 2.

• Annual transvaginal ultrasound and CA-125 measurement starting at age 30-35 or 5-10 years before the earliest age of ovarian cancer diagnosis in your family 4.
• Clinical breast examination twice yearly and annual mammography, as maternal ovarian cancer may indicate broader hereditary cancer risk 2.
• Monthly breast self-examination 2.
• Repeat genetic counseling if new family members develop cancer or if new genetic testing technologies become available 2.

When Prophylactic Surgery Could Be Reconsidered

Prophylactic oophorectomy might be appropriate in specific scenarios even without identified mutation:

• If you are undergoing hysterectomy for benign uterine conditions after age 40, concurrent bilateral salpingo-oophorectomy can be considered to eliminate ovarian cancer risk, as 18.2% of ovarian cancers occur in women who previously had hysterectomy with ovarian preservation 1.
• If additional family members develop ovarian cancer (reaching three or more cases), making hereditary syndrome more likely despite negative testing 1.
• If your mother developed ovarian cancer before age 45, suggesting early-onset hereditary pattern that warrants more aggressive prevention 1.

Risks of Unnecessary Prophylactic Surgery

Prophylactic oophorectomy in premenopausal women without confirmed high-risk mutations causes significant harm:

• Surgical menopause with associated cardiovascular disease risk, osteoporosis, cognitive decline, and sexual dysfunction 5.
• Studies demonstrate overall negative health effects when prophylactic bilateral salpingo-oophorectomy is performed before natural menopause in average-risk women 5.
• Surgical complications occur in 11.5% of women undergoing prophylactic oophorectomy 4.
• Even after prophylactic oophorectomy, a 1-4.3% residual risk of primary peritoneal carcinoma remains 2, 1.