No Survival Advantage for Risk-Reducing Mastectomy Over Surveillance in BRCA1/2 Carriers

In a prospective cohort study of 1205 patients with BRCA1 or BRCA2 pathogenic variants (pvBRCA1/2), bilateral risk-reducing mastectomy (BRRM) significantly lowered the incidence of breast cancer but did not result in a statistically significant improvement in overall survival (OS) or breast cancer-specific survival compared with intensive imaging surveillance. The findings, published in the Journal of Clinical Oncology, suggest that for patients who prioritize breast conservation or wish to avoid the morbidity of major surgery, modern surveillance protocols offer a safe and effective alternative for mortality risk management.¹

Study Design and Incidence Outcomes

The study, led by Ashu Gandhi, MD, and colleagues at the Manchester University NHS Foundation Trust, followed a cohort of 1205 carriers of pvBRCA1/2 over a median period of 9.5 years. Of the participants, 460 (38.2%) elected to undergo BRRM, while 745 (61.8%) chose imaging surveillance. Surveillance protocols were aligned with UK national guidelines, typically involving annual MRI for women aged 30 to 49 and annual mammography for those aged 40 and older.

As expected, BRRM was highly effective at reducing cancer incidence. Only 10 cases of breast cancer were diagnosed in the BRRM group (incidence rate, 2.2%), compared with 138 cases in the surveillance group (incidence rate, 18.5%). This represents a significant reduction in risk (HR, 0.06; 95% CI, 0.03-0.12; P <.001). Of the 10 cancers in the BRRM group, 8 were identified at the time of risk-reducing surgery (occult) and 2 were subsequent primary cancers.

Mortality and Survival Analysis

Despite the dramatic reduction in cancer incidence, the researchers found no statistically significant difference in mortality between the groups. In the surveillance cohort, 15 patients (2.0%) died of breast cancer, while only 1 patient (0.2%) died of breast cancer in the BRRM cohort. While the absolute number of deaths was lower in the surgical group, the difference did not reach statistical significance for breast cancer-specific survival (P =.09) or OS (P =.70).

When analyzing the cohorts by specific gene variants, the results remained consistent. For BRCA1 carriers—who typically face higher-grade, triple-negative tumors—there was no significant OS benefit associated with BRRM (P =.30). For BRCA2 carriers, there were no breast cancer deaths recorded in either the surgical or surveillance groups during the follow-up period.

Clinical Implications for Patient Counseling

The study highlights a critical gap between patient perception and clinical outcomes. Many choose BRRM under the impression that it is necessary for long-term survival. However, the researchers noted that a significant minority of patients express regret following the procedure due to surgical complications, loss of sensation, and impact on body image.

“Patient-reported outcome measures² are similar in women choosing between surveillance or BRRM in psychosocial elements but not in physical well-being, further indicating the potential effects of BRRM and reconstruction on women's physical and sexual well-being,” study authors added.¹

Limitations and Context

The authors acknowledged that longer follow-up (up to 20 years) may be required to detect a potential survival benefit, particularly for BRCA1 carriers. Furthermore, the surveillance cohort utilized high-quality MRI, which may not be accessible in all global clinical settings.

Nonetheless, for clinicians managing high-risk patients, the study provides evidence-based support for a shared decision-making process. The choice between BRRM and surveillance can be framed as a trade-off between the risk of a cancer diagnosis and the physical and psychological impact of surgery, rather than a definitive choice for survival.

REFERENCES

1. Gandhi A, Howell SJ, Harkness EF, et al. Survival outcomes with or without risk-reducing mastectomy in BRCA1 and BRCA2 pathogenic variant carriers. J Clin Oncol. 2026;44(10):[Pagination]. doi:10.1200/JCO-25-00834

2. van Egdom LSE, de Kock MA, Apon I, Mureau MAM, Verhoef C, Hazelzet JA, Koppert LB. Patient-Reported Outcome Measures may optimize shared decision-making for cancer risk management in BRCA mutation carriers. Breast Cancer. 2020 May;27(3):426-434. doi: 10.1007/s12282-019-01033-7. Epub 2019 Dec 12. PMID: 31832891; PMCID: PMC7196093.