Delaying BSO to Age 50 Leaves BRCA1 Carriers With 24% Ovarian Cancer Risk

A 30-year-old BRCA1 carrier who postpones bilateral salpingo-oophorectomy (BSO) until age 50 years faces a projected 23.9% residual risk of ovarian cancer, compared with 4.2% if surgery is performed at age 40 years, according to a prospective cohort study published in JAMA Surgery. For BRCA2 carriers, the same delay carried a projected risk of 3.5%. Residual lifetime risk remained 8.4% for BRCA1 carriers and 3.7% for BRCA2 carriers at age 75 years, which the investigators judged high enough to consider preventive surgery in older women in good health. The estimates do not capture the menopausal harms of BSO, which the authors said should be weighed alongside cancer risk in individualized counseling.

How was the study designed?

Investigators with the Hereditary Ovarian Cancer Clinical Study Group followed 5713 women with a BRCA1 (n = 4286) or BRCA2 (n = 1427) pathogenic variant who were recruited at 24 international centers between 1995 and 2024. Participants were aged 30 to 74 years at baseline (mean [SD] age, 42.0 [10.8] years), had both ovaries intact, and had no history of ovarian cancer. Among women with available data, 37.9% had a personal history of breast cancer and 22.1% reported at least 1 first-degree relative with ovarian cancer. Participants completed follow-up questionnaires every 2 years; mean (SD) follow-up was 4.4 (3.9) years.

The analysis had 2 parts. First, the team calculated age-specific ovarian cancer incidence rates from the cohort. Second, they applied those rates, together with US female mortality rates from the Surveillance, Epidemiology, and End Results (SEER) 17 database (excluding deaths from ovarian and breast cancer), to a life table model. The model projected residual lifetime risk across 130 scenarios defined by variant type, current age (30-75 years), and planned age at BSO or no BSO. It assumed BSO eliminated ovarian cancer risk from the age of surgery onward and that no occult cancers were found at surgery.

What is the lifetime risk of ovarian cancer for BRCA carriers?

During follow-up, 249 incident ovarian cancers were diagnosed: 225 among BRCA1 carriers (5.2%) and 24 among BRCA2 carriers (1.7%). Median (IQR) age at diagnosis was 50.3 (45.0-57.1) years for BRCA1 carriers and 57.5 (53.3-64.8) years for BRCA2 carriers.

Key incidence and risk findings included:

• Annual incidence: 1.18% (95% CI, 1.04-1.34) per person-year for BRCA1 carriers and 0.40% (95% CI, 0.25-0.57) for BRCA2 carriers
• BRCA1 incidence by age: 0.26% per year at ages 35 to 39 years, 1.28% at ages 40 to 44 years, and 3.17% and 3.20% at ages 50 to 54 and 55 to 59 years, respectively
• Actuarial risk from age 30 to 80 years: 56.8% (95% CI, 50.1-62.6) for BRCA1 and 25.4% (95% CI, 15.0-34.5) for BRCA2
• Lifetime risk after accounting for competing mortality: 55.0% (95% CI, 48.8-61.9) for BRCA1 and 24.1% (95% CI, 15.1-36.6) for BRCA2

How does delaying BSO change ovarian cancer risk?

Because lifetime risk is conditional on current age, the authors cautioned that the risk associated with a delayed BSO cannot be derived by subtracting residual risks between 2 ages. They instead modeled each scenario directly.

For a 30-year-old BRCA1 carrier, projected residual risk by planned age at BSO was:

• 35 years: 0.9% (95% CI, 0.6-1.4)
• 40 years: 4.2% (95% CI, 3.1-5.2)
• 45 years: 12.1% (95% CI, 10.0-14.2)
• 50 years: 23.9% (95% CI, 20.7-27.4)
• 55 years: 34.7% (95% CI, 30.9-38.8)
• No BSO: 55.0% (95% CI, 48.8-61.9)

For a 30-year-old BRCA2 carrier, projected residual risk was 1.1% (95% CI, 0.2-2.3) with BSO at 45 years, 3.5% (95% CI, 1.1-6.2) at 50 years, 7.7% (95% CI, 3.7-12.0) at 55 years, and 12.8% (95% CI, 7.7-18.3) at 60 years.

The authors observed that the benefit of BSO was greatest for BRCA1 carriers and declined sharply with older age at surgery, whereas the benefit for BRCA2 carriers was lower and declined more gradually. They noted that the findings align with current recommendations for risk-reducing BSO at age 35 years for BRCA1 carriers and age 45 years for BRCA2 carriers.

Is BSO still worth considering for older BRCA carriers?

Residual lifetime risk declined with current age as competing mortality increased. For BRCA1 carriers, residual risk was 54.8% at age 35 years, 42.7% at age 50 years, 24.7% at age 60 years, and 8.4% (95% CI, 1.7-22.7) at age 75 years. For BRCA2 carriers, corresponding values were 24.2%, 22.2%, 14.3%, and 3.7% (95% CI, 0.1-22.7). Based on SEER data, approximately 34% of 30-year-old women die of another cause before age 80 years; life expectancy at age 75 years was estimated at 11.6 years.

The investigators recommended that discussions with older patients weigh the expected reduction in ovarian cancer risk against comorbidities, life expectancy, and potential surgical and anesthetic complications, and they suggested the age-based table of life expectancy and residual risk as a starting point for shared decision-making. Many women do not undergo genetic testing until later in life, the authors noted, and may question whether surgery still offers benefit.

Do family history and breast cancer history change the estimates?

Among BRCA1 carriers, cumulative ovarian cancer risk differed by family history of ovarian cancer, so the authors provided separate residual risk tables for BRCA1 carriers with and without such history in the online supplement. They advised interpreting those stratified estimates cautiously, especially in older age groups where events were limited. A personal history of breast cancer at baseline was associated with only a modest difference in ovarian cancer risk.

How do salpingectomy and hormone therapy fit into BSO counseling?

Some patients consider bilateral salpingectomy with delayed oophorectomy to postpone surgical menopause. According to the authors, this approach has been associated with improved quality of life compared with BSO among women who do not use menopausal hormone therapy, but it has not been shown to reduce ovarian cancer risk. The NRG Oncology SOROCk trial (NRG-CC008; NCT04251052) is evaluating whether salpingectomy with delayed oophorectomy is noninferior to BSO among BRCA1 carriers aged 35 to 50 years.

For premenopausal women, BSO induces abrupt surgical menopause, with potential effects on vasomotor symptoms, sleep, neurocognitive function, cardiovascular and bone health, mood, sexual functioning, and quality of life. The investigators previously reported that menopausal hormone therapy was safe for BRCA carriers without breast cancer, and that estrogen alone was associated with a lower risk of breast cancer. Hormone therapy is not currently offered to women with a history of breast cancer, and for women with an intact uterus who wish to take unopposed estrogen, hysterectomy at the time of BSO should be discussed.

What are the key takeaways for oncology nurses?

• Anchor timing conversations in age-specific numbers. For a 30-year-old BRCA1 carrier, projected ovarian cancer risk rises from 4.2% with BSO at 40 years to 23.9% at 50 years.
• Distinguish BRCA1 from BRCA2 counseling. Projected risk for a 30-year-old BRCA2 carrier remained at 3.5% or lower with BSO by age 50 years, reflecting later onset of disease.
• Avoid ruling out surgery based on age alone. Residual risk at age 75 years was 8.4% for BRCA1 and 3.7% for BRCA2 carriers; comorbidities, life expectancy, and surgical risk should guide the decision.
• Reinforce that screening is not a substitute for surgery. Serum CA-125 monitoring and transvaginal ultrasound have not been shown to be effective for ovarian cancer screening.
• Prepare patients for surgical menopause. Education on vasomotor, sleep, bone, cardiovascular, cognitive, and sexual health effects, and on hormone therapy eligibility based on breast cancer history, supports informed choices.
• Clarify the evidence on salpingectomy alone. Salpingectomy with delayed oophorectomy has not been shown to reduce ovarian cancer risk; eligible BRCA1 carriers may be referred to ongoing trials such as SOROCk.
• Support early identification. The authors emphasized that expected benefit from BSO is greatest in young, healthy carriers, underscoring the role of timely genetic testing and cascade testing of relatives.

References

1. Giannakeas V, Apostol AI, Diella C, et al; Hereditary Ovarian Cancer Clinical Study Group. Projected benefit of bilateral salpingo-oophorectomy by age in BRCA carriers. JAMA Surg. Published online September 23, 2026. doi:10.1001/jamasurg.2026.4356
2. Kuchenbaecker KB, Hopper JL, Barnes DR, et al; BRCA1 and BRCA2 Cohort Consortium. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402-2416. doi:10.1001/jama.2017.7112
3. A study to compare two surgical procedures in individuals with BRCA1 mutations to assess reduced risk of ovarian cancer. ClinicalTrials.gov identifier: NCT04251052. Updated August 7, 2026. Accessed October 8, 2026. https://clinicaltrials.gov/study/NCT04251052
4. Kotsopoulos J, Seca M, Gronwald J, et al. Menopausal hormone therapy and the risk of breast cancer in women with a pathogenic variant in BRCA1 or BRCA2. J Natl Cancer Inst. 2026;118(5):856-864. doi:10.1093/jnci/djaf363
5. Narod SA, Gronwald J, Karlan B, et al. Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2024;116(11):1753-1760. doi:10.1093/jnci/djae151
6. Henderson JT, Webber EM, Sawaya GF. Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;319(6):595-606. doi:10.1001/jama.2017.21421