Cardiac safety and efficacy of concomitant liposomal doxorubicin, docetaxel, and trastuzumab as neoadjuvant therapy in HER2-overexpressing breast cancer: A retrospective analysis.

Abstract

583 Background: Concurrent therapy of trastuzumab, anthracycline and taxane for the neoadjuvant treatment of breast cancer (BC) results in an improved rate of pathological complete response (pCR). However, there is considerable concern about the cardiac safety of this combination. The use of liposomal doxorubicin might be a valuable alternative with lower cardiotoxicity. We report cardiac safety and pCR-rate of a single arm, retrospective, multicenter analysis of neoadjuvant treatment for BC with liposomal doxorubicin, trastuzumab, and docetaxel. Methods: In this study 84 women with BC and HER2 overexpression were investigated in 3 oncological departments in Austria. All patients were treated with liposomal doxorubicin (50 - 60 mg/m²), docetaxel (75 mg/m²) and concurrent with trastuzumab for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥ 55%. Cardiac function was by LVEF and was examined at regular intervals(cycles 0-3, cycle 6, FU). Clinical response was evaluated by diagnostic breast imaging after cycles 3 and 6. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 2.4 years. Results: Median age of the patients was 50 years. After 6 cycles of treatment the pCR rate was 46%. In this cohort a negative estrogen-and/or progesteron receptor was predictive for pCR (p<0.001). No patient progressed during treatment. None of the patients suffered symptomatic heart failure. Only one patient (1.6%) with asymptomatic LVEF of 45% was observed during follow-up. Conclusions: In this multicenter analysis we observed a considerably high rate of pCR in HER2-positive BC treated with liposomal doxorubicin, docetaxel and trastuzumab. The addition of liposomal doxorubicin instead of conventional doxorubicin or epirubicin entails a very favorable cardiotoxicity profile. This regimen is a safe treatment option in patients with HER-2 positive breast cancer.