Gauging Benefits of Risk-Reducing Surgery for BRCA-Related Ovarian Cancer

Older age should not discourage healthy women with a genetic risk for ovarian cancer from considering risk-reducing bilateral salpingo-oophorectomy (BSO), investigators in a study of BRCA carriers concluded.

A 30-year-old BRCA1 carrier who delayed BSO to age 50 still had a 23.9% lifetime risk of ovarian cancer. By age 75, residual risk had declined to 8.4% for a BRCA1 carrier and 3.7% for a BRCA2 carrier. Actuarial risk calculations to age 80 showed that BRCA1 carriers had a 56.8% lifetime risk of developing ovarian cancer, and BRCA2 carriers had a 25.4% risk.

The risk estimates exceed those of previous studies, reported Vasily Giannakeas, PhD, of Sinai Health System in Toronto, and colleagues in JAMA Surgery.

“These findings support individualized counseling about BSO timing that incorporates residual lifetime ovarian cancer risk in addition to other important factors, including breast cancer history, menopausal harms, fertility goals, and patient preferences,” the authors stated. “Although these [actuarial] tables quantify residual ovarian cancer risk, they do not estimate the overall net benefit of BSO because factors such as cardiovascular, bone, cognitive, vasomotor, mental health, and quality-of-life outcomes after early menopause were not modeled.”

“For older women, the discussion about BSO should consider whether the expected reduction in ovarian cancer risk justifies surgery in the context of a patient’s comorbidities, life expectancy, and possible surgical and anesthetic complications,” they wrote.

The residual risk for older women in good health is “sufficiently high” to consider preventive surgery, potentially reaching the level of “substantial risk” for BRCA1 carriers who defer BSO until age 50, they added.

Many high-risk patients delay risk-reducing surgery because of perceived trade-off between risk reduction and quality of life, according to the authors of an accompanying commentary. The impact of BSO on childbearing potential could be reduced by improved access and coverage for fertility specialists and oocyte cryopreservation. Quality-of-life concerns about premature surgical menopause could be addressed by appropriate patient counseling and education about menopausal hormone therapy.

“Interval salpingectomy with delayed oophorectomy is a promising strategy with the potential for tubo-ovarian cancer risk reduction without the added burden of surgical menopause and allowing retention of fertility potential,” wrote Kara C. Long, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues. “Data suggest up to an 80% reduced risk of tubo-ovarian cancer in the general population after salpingectomy.”

The strategy is being evaluated in two large ongoing clinical trials, they added.

The study by Giannakeas and colleagues can help inform discussions about the timing of risk-reducing BSO, said Karen Lu, MD, of Moffitt Cancer Center in Tampa, Florida. Both the National Comprehensive Cancer Network and the Society of Gynecologic Oncology have recommended age ranges for BSO, 35-40 for BRCA1 carriers and 40-45 for BRCA2 carriers.

“Especially as we see more ‘previvors’ — young women with an increased risk of cancer but no personal history of cancer — we must continue to have more information to counsel appropriately around risk-reducing salpingo-oophorectomy, a procedure which dramatically decreases ovarian cancer risk but comes with certain quality of life consequences,” Lu told MedPage Today.

The study has several messages for clinicians who care for patients with genetic risk for ovarian cancer, added Monica Avila, MD, also of Moffitt Cancer Center.

“The highest risk described for BRCA1 is 30-35 and 30-40 for BRCA2, consistent with prior literature rates and age cut-offs for national recommendations to undergo optimal risk reducing surgery,” said Avila. “The risk of developing ovarian cancer in BRCA patients decreases over time, particularly after menopause, but that risk is not zero, and risk-reducing surgery is still the standard of care, even if patients present later in life. The earlier we identify the risk, the better the chance of intervening and preventing an ovarian cancer death.”

Giannakeas and colleagues conducted a prospective cohort study to investigate an unresolved issue regarding risk-reducing BSO: lack of guidance about upper age limits at which BSO is no longer advisable.

Study participants were recruited from 1995 to 2024 at 24 international centers and followed for an average of 4.4 years. Investigators performed life table analysis using age-specific ovarian cancer incidence and competing mortality to estimate lifetime ovarian cancer risk among women with a BRCA1 or BRCA2 pathogenic variant.

The analysis included 4,286 BRCA1 carriers and 1,427 BRCA2 carriers ages 30 to 74 (mean age 42.0) with intact ovaries and no history of ovarian cancer. The analysis accounted for data suggesting that 34% of 30-year-old women would die of competing causes before age 80. Subsequently, 249 participants developed ovarian cancer, translating into annualized incidence of 1.18% per person-year for BRCA1 carriers and 0.40% for BRCA2 carriers.

The expected benefit of BSO decreased steadily from age 30 to 75. For BRCA1 carriers, the residual risk for BRCA1 carriers was 54.8% at age 35, 42.7% at 50, and 8.4% at 75. Corresponding residual risk for BRCA2 carriers was 24.2%, 22.2%, and 3.7%.