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To determine whether clinical outcome is different between BRCA-mutated versus non–BRCA-mutated breast cancer, U.K. investigators conducted a prospective cohort study (POSH) of 2733 young women (median age, 36 years) who received a histologic diagnosis of invasive breast cancer between 2000 and 2008 and were evaluated for BRCA mutations. A total of 338 (12%) had BRCA mutations, of which 60% were BRCA1 and 40% were BRCA2.
During the time of study recruitment, BRCA testing and risk-reducing surgery were not routinely recommended in the U.K. Of the cohort, 90% received adjuvant chemotherapy, and equal fractions received mastectomy or breast-conserving therapy. Patients were followed for more than 8 years on average, during which time 651 breast-cancer deaths had occurred.
Overall survival (OS) was similar between those harboring a BRCA mutation and those with sporadic breast cancer at 2 years (97.0% and 96.6%, respectively), 5 years (83.8% and 85.0%), and 10 years (73.4% and 70.1%). Of note, a large subset of patients (558) with triple-negative breast cancer (TNBC) seemed to have an OS advantage at 2 years, but not at 5 or 10 years.
Copson ER et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): A prospective cohort study. Lancet Oncol 2018 Jan 11; [e-pub]. (http://dx.doi.org/10.1016/S1470-2045(17)30891-4)
Comment
These findings assure us that the prognosis is similar with BRCA-mutated breast cancer or sporadic breast cancer. That said, emerging data suggest that older agents such as platinum chemotherapy incorporated into adjuvant programs may confer benefit for patients with BRCA-mutated disease, particularly in TNBC. Also, PARP inhibitors are being studied in adjuvant trials for patients with early-stage, BRCA-mutated tumors. It is likely, and hoped, that the results of ongoing clinical trials involving novel agents in the adjuvant setting will ultimately lead to distinct treatments for women with BRCA-mutated tumors.