BRCA Mutation Has Little Effect on Outcome with Neoadjuvant Therapy

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A retrospective analysis to determine the efficacy of neoadjuvant systemic therapy for breast cancer patients with and without BRCA mutations found the overall prognosis was similar in both groups of patients. “No significant differences were noted in survival outcomes with respect to BRCA status and type of [neoadjuvant systemic therapy] received,” reported investigators from the University of Texas MD Anderson Cancer Center in Houston.1

The researchers identified 317 women with breast cancer who underwent clinical genetic testing for BRCA 1 and BRCA2 mutations and received neoadjuvant therapy. Of these, 237 tested negative for mutations (the “noncarriers”); 57 were found to be BRCA1 mutation carriers and 23 to be BRCA2 mutation carriers. Overall, 26% achieved a pathologic complete response after neoadjuvant systemic therapy. “The [pathologic complete response] rate was significantly higher in BRCA1 carriers (46%) compared with BRCA2 carriers (13%) and noncarriers (22%; P = .001),” the investigators stated in the Journal of Clinical Oncology.

BRCA status did not significantly influence overall or relapse-free survival. Estimated 5-year overall survival rates were 90% in the noncarrier group vs 87% in the BRCA1 group and 100% in the BRCA2 group. Estimated overall 5-year relapse-free survival was 74%, with 73% in noncarriers vs 72% in the BRCA1 group and 93% in the BRCA2 group. Patients who achieved a [pathologic complete response] had a better relapse-free survival (93%) than those who did not (68%).

On multivariate analysis independent predictors of pathologic complete response were BRCA1 status, estrogen receptor (ER) negativity, and concurrent trastuzumab use.

“Our data indicate that BRCA1 status and ER negativity are independently associated with higher [pathologic complete response] rates after neoadjuvant systemic therapy. Importantly, overall prognosis of breast cancer in BRCA mutation carriers is similar to that of sporadic breast cancers, despite their identification with initial poor prognostic features,” the authors concluded.

Accompanying Commentary

The report “underscores the fact that it is still not known whether a distinct treatment approach should be recommended to women with BRCA1/2 mutation–associated breast cancer outside the context of a clinical trial,” Mark E. Robson, MD, of Memorial Sloan-Kettering Cancer Center, noted in an editorial commenting on whether BRCA1/2 mutations should influence treatment selection.2 He stated that excellent results of anthracycline-taxane therapy in the study “support the continued use of regimens containing these agents in the treatment of early-stage breast cancer in BRCA1 carriers. ■


1. Arun B, et al: J Clin Oncol 29:3739-3746, 2011.

2. Robson ME: J Clin Oncol 29:3724-3726, 2011.