Primary chemotherapy for operable breast cancer: the NSABP experience

NSABP Protocol B-18 was designed to compare pre-operative chemotherapy with doxorubicin (adriamycin) and cyclophosphamide (AC) given every 3 weeks for four cycles versus the same chemotherapy treatment given in the adjuvant setting. In protocol B-18, 1523 women with operable breast cancer were randomized to receive four cycles of AC followed by surgery or surgery followed by four cycles of AC. Women 50 years of age or older also received tamoxifen for 5 years, starting after chemotherapy.Subsequently, NSABP Protocol B-27 was conducted with the intent to determine the effect of adding docetaxel (taxotere [T]) after four cycles of preoperative AC on disease-free survival (DFS) and overall survival (OS) of women with operable breast cancer. A total of 2411 women with operable primary breast cancer were randomized to receive either four cycles of preoperative AC followed by surgery (group I) or four cycles of AC followed by four cycles of T, followed by surgery (group II), or four cycles of AC followed by surgery and then four cycles of T (group III). Tamoxifen was given to all patients, starting concurrently with chemotherapy.In protocol B-18, mean tumor size was 3.5 cm. Preoperative AC produced objective clinical responses in 79% of the treated patients and clinical complete responses (cCR) in 36%. Pathologic complete responses (pCR, defined as no invasive cancer in the breast) were observed in 13%. OS and DFS were similar in the two randomized treatment groups. Preoperative chemotherapy resulted in a statistically significant increase in the rate of breast conserving therapy (BCT), from 60% to 68%. This was particularly notable in the patients with tumors >5 cm, in whom BCT was increased from 8% to 22% [1]. Although there was a trend toward increased ipsilateral breast tumor recurrence (IBTR) in preoperative chemotherapy patients who were downstaged to lumpectomy compared with patients treated preoperatively who were considered to be candidates for BCT at the outset