The purpose of this study is to evaluate the efficacy and safety of a biweekly neoadjuvant docetaxel/gemcitabine regimen in patients with histologically confirmed stage II and III breast cancer. In addition, a cDNA microarray study attempted to correlate pretreatment gene-expression profile with clinical and pathologic responses. Docetaxel 65 mg/m(2) was given in a 60-minute intravenous infusion followed by gemcitabine 2,500 mg/m(2) in a 30-minute intravenous infusion every 2 weeks for six cycles; prophylaxis with growth factors was allowed. Four cycles of standard AC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)every 21 days) was routinely delivered to all patients postsurgery. Thirty patients are accrued on-study so far. The overall response rate for 24 evaluable patients was 79% (95% confidence interval, 9.7 to 53.5) with six complete responses and 13 partial responses. One patient (4%) out of 23 achieved a pathologic complete response in the breast at the time of definitive surgery. Breast conservation procedure was possible in 14 patients (61%). A total of 161 cycles has been delivered. Grade 1/2 alopecia and a mild grade 1/2 LDH increase were the most frequently reported adverse events (78% and 55% of cycles, respectively). Grade 3/4 neutropenia was reported in 18 cycles (11%). These preliminary results show that biweekly docetaxel and gemcitabine is an optimal regimen as neoadjuvant treatment of stage II and III breast cancer. In spite of the large tumor size, breast conservation was possible in 61% of the patients. In general, toxicity was very manageable.