This trial was designed to compare the efficacy of paclitaxel with that of docetaxel and to compare the standard taxane schedule (every 3 weeks) with a weekly schedule in nearly 5000 women with axillary lymph node–positive or high-risk, lymph node–negative breast cancer. We found no significant differences in survival between the groups treated with paclitaxel and those treated with docetaxel or between the groups treated weekly and those treated every 3 weeks. However, the interpretation of our results is complicated by an unanticipated interaction between the type of taxane administered and the treatment schedule for the group receiving weekly docetaxel. In a comparison of the three experimental groups with the group receiving standard paclitaxel treatment, the group receiving weekly paclitaxel and the group receiving docetaxel every 3 weeks had significantly improved disease-free survival, and the group receiving weekly paclitaxel had significantly improved overall survival. In comparison with the group receiving standard therapy, the group receiving weekly paclitaxel had significantly more moderate-to-severe neuropathy and the group receiving docetaxel every 3 weeks had significantly more severe neutropenia and its associated complications. The 32% reduction in the hazard ratio for death afforded by weekly paclitaxel is similar to that observed for anthracycline-containing chemotherapy as compared with no adjuvant cytotoxic therapy.1
The results are consistent with studies of metastatic breast cancer that demonstrated a benefit of weekly paclitaxel7
or docetaxel every 3 weeks,6
as compared with paclitaxel every 3 weeks.
A similar benefit was not observed for the group receiving weekly docetaxel, a result that may be attributable in part to the less acceptable adverse-events rates and poorer adherence to treatment in this group. The findings are also consistent with the results of trials of metastatic breast and prostate cancer that indicate that docetaxel may be more effective if given every 3 weeks rather than weekly.11,12
The results were not changed when the data were analyzed according to definitions of end points similar to those used in other trials evaluating paclitaxel.2-4
Guidelines for standardization of end-point definitions in trials of adjuvant breast-cancer treatment have recently been proposed that we think should be routinely incorporated into future trials.13
Other studies have suggested that the benefits of taxane-based therapy are driven largely by improved outcomes in hormone receptor–negative disease7,12
or HER2-positive disease and that there may be little if any benefit of taxane therapy for the 50% or more of patients with hormone receptor–positive, HER2-negative disease.9
In our trial, there were similar trends favoring weekly paclitaxel in patients with HER2-negative disease that was either hormone receptor–positive or hormone receptor–negative. Although hormone-receptor status was not determined centrally, analysis of an another ECOG-coordinated Intergroup trial conducted during a similar time period demonstrated 90% concordance for hormone-receptor expression between local laboratories and a central laboratory, and 95% concordance for tumors determined to be HER2-negative in local laboratories.14
Another study, which comand cyclophosphamide every 3 weeks with four cycles of fluorouracil, epirubicin, and cyclophosphamide followed by weekly paclitaxel for 8 weeks, also showed a better outcome in patients treated with weekly paclitaxel, including patients with hormone receptor–positive or hormone receptor–negative disease, as determined by testing in a central laboratory according to a prespecified analysis plan.15
Taken together, these results suggest that the benefits are similar in hormone receptor–positive and hormone receptor–negative breast cancer.
In conclusion, treatment with doxorubicin and cyclophosphamide followed by weekly paclitaxel is associated with improved disease-free survival and overall survival in comparison with treatment with doxorubicin and cyclophosphamide followed by paclitaxel given every 3 weeks. We found no evidence that women with hormone receptor–positive, HER2-negative breast cancer derived less benefit than those with breast cancer negative for hormone receptors or positive for HER2.