Germline BRCA Mutation and Outcomes in Young-Onset Breast Cancer
In the POSH study in the UK population reported in The Lancet Oncology, Copson et al found women with young-onset breast cancer who carry a germline BRCA mutation have survival similar to noncarriers, and BRCA-mutation carriers vs noncarriers with triple-negative breast cancer may have an early survival advantage.
Study Details
The prospective cohort study involved data from 2,733 women from 127 sites in the UK aged ≤ 40 years at first diagnosis of invasive breast cancer between January 2000 and January 2008. Patients were identified within 12 months of initial diagnosis. Patients with a previous invasive malignancy, except nonmelanoma skin cancer, were excluded.
Pathogenic BRCA mutations were identified in 338 patients (12%), including 201 with BRCA1 and 137 with BRCA2. Long-term follow-up of the cohort is ongoing.
Overall Survival
After a median follow-up of 8.2 years, there were 678 deaths, with 651 (96%) due to breast cancer. On a multivariate analysis, there were no significant differences in overall survival between BRCA-positive and BRCA-negative patients at 2 years (97.0% vs 96.6%), 5 years (83.8% vs 85.0%), or 10 years (73.4% vs 70.1%; overall hazard ratio [HR] = 0.96, P = .76). Among 558 patients with triple-negative breast cancer, BRCA-mutation carriers had better overall survival vs noncarriers at 2 years (95% vs 91%, HR = 0.59, P = .047) but not at 5 years (81% vs 74%, HR = 1.13, P = .62) or 10 years (72% vs 69%, HR = 2.12, P = .12) on a multivariable analysis flexible parametric survival model.
The investigators concluded: “Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences.”
The study was funded by Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and PPP Healthcare Medical Trust Grant.
Diana M. Eccles, MD, of the University of Southampton and University Hospital Southampton NHS Foundation Trust, is the corresponding author of The Lancet Oncology article.
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