ANZ 0502 Neoadjuvant Gemcitabine

All patients will receive 4 cycles of epirubicin (90mg/m2, IV, Day 1) and cyclophosphamide (600mg/m2 IV, Day 1) followed by 4 cycles of Taxotere™ (docetaxel, 75mg/m2, IV, Day 1) and Gemzar® (gemcitabine, 1000mg/m2 IV, Days 1 & 8), with the addition of Herceptin® (trastuzumab) if the tumour is HER2 positive (trastuzumab: Cycle 1: 4mg/kg IV day 1, 2mg/kg IV day 8 & 15; Cycles 2-4, 2mg/kg IV day 1, 8 & 15; 6mg/kg IV day 22 of Cycle 4). Trastuzumab will be given for a total duration of one year (13 x 3 weekly cycles). Larger operable and locally advanced tumours are associated with a poorer prognosis and a high risk of micrometastatic disease and require aggressive multimodality therapy. Anthracycline-based chemotherapy remains the core of most pre or postoperative chemotherapy regimens for early or locally advanced breast cancer unless contraindicated. Given promising data, including the established benefit of docetaxel in the adjuvant setting and the use of gemcitabine in metastatic breast cancer, suggesting non-cross resistance and synergy with the taxanes, a phase II study consisting of 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of docetaxel (day 1) and gemcitabine (day 1 & 8) each cycle delivered every three weeks is proposed. For patients with HER2 overexpressing breast cancer, the addition of trastuzumab to the docetaxel and gemcitabine treatment cycles aims to maximize synergy seen between all three agents and minimize cardiac toxicity. These regimens aim to maximize the pathologic complete response rate (pCR) rate which may translate into a survival benefit in the long term. Breast cancer tissue will also be obtained to correlate clinical and pathologic response with changes in molecular parameters.