A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer.

OBJECTIVE We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer. METHODS This prospective clinical study was a pilot involving 63 female patients. Before surgery, patients with tumors overexpressing human epidermal growth factor receptor 2 received four cycles of 60 mg/m(2) anthracycline and 600 mg/m(2) cyclophosphamide every 3 weeks, whereas those whose tumors did not overexpress human epidermal growth factor receptor 2 received four cycles of 75 mg/m(2) docetaxel and 600 mg/m(2) cyclophosphamide every 3 weeks. A quasi-pathological complete response (i.e. absence of invasive tumor or only focal residual tumor cells) was the primary endpoint, with compliance and predictors for each regimen as secondary endpoints. If a quasi-pathological complete response was not achieved, then crossover to the alternative treatment was recommended. RESULTS The quasi-pathological complete response rate was 36.5% (23 of 63) overall, 27.8% (5 of 18) for the anthracycline and cyclophosphamide regimen and 40.0% (18 of 45) for the docetaxel and cyclophosphamide regimen. Docetaxel and cyclophosphamide treatment induced a quasi-pathological complete response in most patients with triple-negative tumors (15 of 19). The relative dose intensity was 97.3% for the anthracycline and cyclophosphamide regimen and 96.6% for the docetaxel and cyclophosphamide regimen. Quasi-pathological complete response to the docetaxel and cyclophosphamide regimen was associated with low estrogen receptor and progesterone receptor expression and high MIB-1 and topoisomerase IIalpha expression, in univariate analyses, but only with low estrogen receptor expression in multivariate analysis. CONCLUSIONS Selecting neoadjuvant chemotherapy regimens on the basis of individual human epidermal growth factor receptor 2 status improved efficacy, with docetaxel and cyclophosphamide treatment showing particular promise in tumors with the potential to be highly malignant.