In a groundbreaking retrospective cohort study published in The Lancet Oncology, researchers at the University of Cambridge have delivered compelling evidence demonstrating that bilateral salpingo-oophorectomy (BSO)—the surgical removal of ovaries and fallopian tubes—substantially reduces the risk of premature death in women harboring pathogenic variants of the BRCA1 and BRCA2 genes who have previously been diagnosed with breast cancer. This procedure, already established as an effective strategy for dramatically decreasing ovarian cancer risk, now gains renewed importance as its long-term survival benefits and safety profile are illuminated through an innovative analysis of linked electronic health records spanning thousands of patients.
Women who carry deleterious mutations in the BRCA1 and BRCA2 genes are known to face markedly elevated lifetime risks of both breast and ovarian cancers, often prompting early preventative interventions. Clinical guidelines currently recommend that these at-risk individuals undergo risk-reducing surgeries such as BSO relatively early in adulthood—typically between ages 35 and 40 for BRCA1 carriers, and between 40 and 45 for BRCA2 carriers—to mitigate the aggressive threat ovarian cancer presents. While BSO has been widely recognized to curtail ovarian cancer incidence by approximately 80%, its overall impact on all-cause mortality, particularly in those with prior breast cancer diagnoses, alongside potential systemic side effects, had remained uncertain until now.
This uncertainty stems partly from the physiological consequences of surgically induced menopause, as the abrupt cessation of ovarian estrogen production precipitates a range of metabolic, cardiovascular, and psychological changes. Notably, hormone replacement therapy—commonly prescribed to alleviate menopausal symptoms—is often contraindicated or cautiously approached in breast cancer survivors due to concerns over hormone-sensitive tumor recurrence. Thus, evaluating BSO’s net clinical benefit in BRCA1 and BRCA2 mutation carriers with prior breast cancer is particularly challenging, rendering randomized controlled trials ethically and practically unfeasible.
Faced with this methodological impasse, the research team capitalized on the power of big data, leveraging comprehensive electronic health records curated by the National Disease Registration Service (NDRS) in NHS England. Through meticulous data linkage to genetic testing results, clinical outcomes, and longitudinal follow-up, they constructed a robust retrospective cohort comprising approximately 3,400 women known to carry BRCA1 or BRCA2 pathogenic variants and previously diagnosed with breast cancer. Of these, nearly 1,850 individuals had undergone BSO, allowing a detailed comparative survival analysis between operated and non-operated groups over a median follow-up period exceeding five years.
The study’s statistical analyses unveiled a striking reduction in the risk of death from any cause among women who chose BSO, with hazard ratios approximating 0.5, signaling a 50% lower likelihood of mortality compared to those who did not undergo the surgery. The survival advantage was even more pronounced in BRCA2 mutation carriers, exhibiting a 56% reduction in mortality risk, while BRCA1 carriers demonstrated a 38% reduction. Beyond mortality, the surgery was associated with a 40% drop in the incidence of secondary cancers, underscoring its protective effect beyond ovarian cancer prevention.
Crucially, the investigators addressed longstanding concerns regarding BSO-induced comorbidities by analyzing rates of cardiovascular disease, cerebrovascular events, and depression. Contrary to reports from general population studies that linked early oophorectomy with heightened risks of heart disease and stroke, this study found no statistically significant association between BSO and these adverse long-term outcomes within the BRCA-mutated breast cancer cohort. Furthermore, mental health outcomes did not deteriorate, alleviating fears of increased depression linked to surgical menopause in this vulnerable population.
These findings mark a pivotal advance in the clinical management of women at genetic risk for gynecological and breast cancers. As Hend Hassan, the study’s lead author and a PhD candidate in Cambridge’s Centre for Cancer Genetic Epidemiology, articulated, the results offer reassurance that the pronounced survival benefits of BSO substantially outweigh the potential menopausal side effects feared by patients and clinicians alike. This clarity empowers both patients and healthcare providers to make more informed, evidence-based decisions regarding prophylactic surgery.
However, the research also shed light on inequities in healthcare access and decision-making. The data revealed that white women were significantly more likely to receive BSO than their Black and Asian counterparts, with the latter groups having approximately half the surgery uptake rate. Additionally, socioeconomic disparities emerged, as women residing in less deprived areas underwent BSO more frequently than those from highly deprived communities. These observations highlight urgent public health needs to elucidate and address the sociocultural, economic, and systemic barriers that impede equitable delivery of life-saving interventions.
Antonis Antoniou, senior author of the study and Director of the Cancer Data-Driven Detection programme at Cambridge, emphasized that the results will transform clinical guidelines and counseling approaches. By quantifying the substantial survival benefit and alleviating fears about serious side effects, the study equips practitioners with solid scientific footing to recommend BSO confidently to eligible patients. Furthermore, the research exemplifies the immense value of integrated NHS datasets for conducting large-scale, impactful, and clinically relevant epidemiological studies.
This investigation’s innovative methodology—exploiting carefully linked, real-world health records complemented by genetic testing data—circumvents ethical constraints surrounding randomized trials and illustrates a new frontier for precision medicine research. The capacity to generate robust evidence at scale, particularly in rarer high-risk subpopulations, promises accelerated discovery and refinement of personalized preventive strategies across oncology and beyond.
Funded primarily by Cancer Research UK, with critical support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre, this study not only advances scientific understanding but also aligns closely with ongoing translational efforts. The University of Cambridge’s partnership in establishing the Cambridge Cancer Research Hospital underscores a broader commitment to harnessing cutting-edge research to transform patient outcomes in the UK and internationally.
In sum, this landmark research definitively supports the recommendation of bilateral salpingo-oophorectomy for BRCA1 and BRCA2 mutation carriers with prior breast cancer, confirming significant improvements in survival and reduction in secondary cancer risk without exacerbating cardiovascular or mental health burdens. As the medical community integrates these insights into practice, the hope is to redress disparities in access and empower more women to benefit from this potentially life-saving procedure.
Subject of Research: People
Article Title: Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records
News Publication Date: 8-May-2025
Web References:
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00156-1/fulltext
http://dx.doi.org/10.1016/S1470-2045(25)00156-1
References:
Hassan, H et al. Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records. Lancet Oncology; 7 May 2025; DOI: 10.1016/S1470-2045(25)00156-1
Keywords: Cancer, Breast cancer, Ovarian cancer
