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% . 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 (15.9% versus 9.9%), this difference was not statistically significant after controlling for patient age and tumor size . Patients in the preoperative chemotherapy group who experienced a pCR had significantly improved DFS and OS compared with all other patients in the preoperative chemotherapy group (P < 0.0001). Clinical response was also associated with improved outcomes with long-term follow up [2, 3].
For protocol B-27, mean tumor size was 4.5 cm; this and other key characteristics were evenly balanced among the three treatment arms. The addition of docetaxel preoperatively resulted in significant increases in cCR and pCR at the time of surgery compared with AC alone (63.6% versus 40.1% and 26.1% versus 13.7%, respectively) . Despite this, addition of docetaxel to AC did not significantly impact on survival in this cohort of patients . There was a trend toward improved DFS in group II patients who received preoperative T, but this was not statistically significant (72% versus 67% DFS at 5 years; HR = 0.86, P = 0.10). In an analysis of relapse-free survival (RFS), which did not include second primary cancers, group II had a significantly better outcome compared with group I (74% versus 69% RFS at 5 years; HR = 0.81, P = 0.03). Group III RFS was not significantly different from group I (71% at 5 years; HR = 0.91, P = 0.32). Addition of docetaxel significantly reduced the incidence of local recurrences as first events, including IBTR in patients treated with breast conservation. There were no significant interactions between treatment and estrogen receptor status, age, tumor size, or clinical nodal status. An exploratory analysis of treatment effects in subsets of patients according to clinical response to AC suggests that preoperative T, but not postoperative T, significantly increased DFS in patients who had a partial clinical response after four cycles of AC (63%, 74%, 65% at 5 years for groups I, II, and III; HR = 0.68 for group II versus group I, P = 0.003). Addition of T did not appear to be beneficial in patients who were nonresponders after AC nor in those patients who had a cCR after AC. Pathologic complete response was a highly significant predictor of DFS and OS in all treatment groups (HR = 0.45, P < 0.0001, and HR = 0.33, P < 0.0001, respectively). In addition, pathologic nodal status after chemotherapy was a significant prognostic factor for survival, independent of pathologic response in the breast.