The treatment of inflammatory breast cancer includes preoperative anthracycline-based chemotherapy, surgery, and radiation therapy. In the past few years, taxanes, mainly paclitaxel, have been frequently used for preoperative chemotherapy, usually in sequence with anthracyclines. The purpose of this retrospective analysis was to determine how adding paclitaxel to anthracycline-based regimens affects prognosis. A total of 240 patients treated in 6 consecutive trials between 1973 and 2000 were included in the analysis. Group 1 (N = 178) consisted of patients treated in the first 4 trials (1973-1993) with FAC (5-fluorouracil/doxorubicin/cyclophosphamide)— based regimens. Group 2 (N = 62) consisted of patients treated in the last 2 trials (1994-2000) with FAC followed by paclitaxel given every 3 weeks or given in a high-dose weekly schedule. The 2 groups differed with respect to median follow-up durations, which were 148 months (range, 85-283 months) in group 1 and 45 months (range, 21-99 months) in group 2. Estrogen receptor (ER) status was negative in 58 cases (33%) in group 1 and 40 cases (65%) in group 2. There was no difference in median age between the groups. The objective response rates (complete and partial) were similar (group 1, 74%; group 2, 82%). The median overall survival (OS) and progression-free survival (PFS) were better in the patients treated with paclitaxel, and these differences reached statistical significance in the patients with ER-negative disease (median OS: group 1, 32 months; group 2, 54 months; P = 0.03; median PFS: group 1, 18 months; group 2, 27 months; P = 0.04). It may be concluded that the addition of paclitaxel to anthracycline-based therapy resulted in a statistically significant improvement in outcome in patients with ER-negative inflammatory breast cancer.