Abstract

Purpose: The National Surgical Adjuvant Breast and Bowel Project Protocol B-27 was designed to determine the effect of adding docetaxel after four cycles of preoperative doxorubicin and cyclophosphamide (AC) on clinical and pathological response rates and on disease-free and overall survival of women with operable breast cancer. Patients and Methods: Women (N = 2,411) with operable primary breast cancer were randomly assigned to receive either four cycles of preoperative AC followed by surgery (group I), or four cycles of AC followed by four cycles of docetaxel, followed by surgery (group II), or four cycles of AC followed by surgery and then four cycles of docetaxel (group III). Clinical and pathologic tumor responses to preoperative therapy were assessed. Results: Mean tumor size (4.5 cm) and other key characteristics were evenly balanced among the three treatment arms. Grade 4 toxicity was observed in 10.3% of 2,400 patients during AC treatment, and in 23.4% of 1584 patients during docetaxel treatment. Compared to preoperative AC alone, preoperative AC followed by docetaxel increased the clinical complete response rate (40.1% v 63.6%; P < .001), the overall clinical response rate (85.5% v 90.7%; P < .001), the pathologic complete response rate (13.7% v 26.1%; P < .001), and the proportion of patients with negative nodes (50.8% v 58.2%; P < .001). Pathologic primary breast tumor response was a significant predictor of pathologic nodal status (P < .001). Conclusion: The addition of four cycles of preoperative docetaxel after four cycles of preoperative AC significantly increased clinical and pathologic response rates for operable breast cancer.