Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer

Abstract

Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine-vinorelbine (GEV) peri-operatively in LABC. Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100mg/m(2), d1q2w) followed by three DOC (100mg/m(2), d1q3w); surgery 3-4weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR). Fifty-six women, aged 32-75 (median 52years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62months, median OS has not yet been reached, while median TTR was 42months. OS was longer in patients with clinical (p=0.004) and pathological response (p=0.002), RT (p<0.0001) and post-operative DOC (p=0.038). TTR was favorably affected by pR (p<0.0001), RT (p<0.0004) and post-operative DOC (p=0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status. The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management.