Pathologic Complete Response After Neoadjuvant Chemotherapy Plus Trastuzumab Predicts Favorable Survival in Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: Results From the TECHNO Trial of the AGO and GBG Study Groups

Abstract

Purpose To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)–overexpressing breast cancer. Patients and Methods Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m2) followed by four 3-week cycles paclitaxel (175 mg/m2) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue. Results Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure. Conclusion Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.