BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

Abstract

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Trial registration: ClinicalTrials.gov NCT00567554.

Figures

Fig 1.

Patient selection. EC, epirubicin/cyclophosphamide; ECB, epirubicin/cyclophosphamide/bevacizumab; T, docetaxel; TB, docetaxel/bevacizumab.

Fig 2.

Kaplan-Meier curves for disease-free survival (DFS). (A) Comparison of DFS in all patients (hazard ratio [HR], 0.644; 95% CI, 0.415 to 0.998; P = .047). (B) Comparison of the effects of pathologic complete response (pCR) on the DFS. The HR for pCR in mutation carriers was 0.74 (95% CI, 0.32 to 1.69; P = .472); the HR for pCR in patients without mutations was 0.18 (95% CI, 0.11 to 0.31; P < .001). The interaction test showed a P value of .005. (C) Comparison of DFS relative to the treatment arm and mutation status. The HRs for bevacizumab treatment were 1.39 (95% CI, 0.61 to 3.15; P = .428) in patients with a BRCA1/2 mutation and 1.02 (95% CI, 0.74 to 1.40; P = .903) in patients without a BRCA1/2 mutation. P(interaction) = .451.

Fig 3.

Pathologic complete response (pCR) rates relative to BRCA1/2 mutation status and treatment arm. BEV, bevacizumab; mut, mutation; wt, wild type.

Fig A1.

Kaplan-Meier curves for distant disease-free survival (DDFS). (A) Comparison of DDFS in all patients. Hazard ratio (HR), 0.554 (95% CI, 0.329 to 0.933; P = .024). (B) Comparison of the effects of pathologic complete response (pCR) on the DDFS. The HR for pCR in mutation carriers was 0.74 (95% CI, 0.27 to 1.98; P = .541); the HR for pCR in patients without mutations was 0.19 (95% CI, 0.10 to 0.34; P < .001). The interaction test showed a P value of 0.0195. (C) Comparison of DDFS relative to the treatment arm and mutation status. The HRs for bevacizumab treatment were 0.97 (95% CI, 0.36 to 2.60; P = .947) in patients with a BRCA1/2 mutation and 1.15 (95% CI, 0.81 to 1.64; P = .432) in patients without a BRCA1/2 mutation. P(interaction) = .756.