Phase II Trial of Preoperative Chemotherapy for Breast Cancer: Japan Breast Cancer Research Network (JBCRN)-02 Trial

Background: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. Patients and Methods: Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2), and cyclophosphamide: 500 mg/m2) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m2) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). Results: The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER-, HER2(+)/ER+, HER2(-)/ER-, and HER2(-)/ER+ patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (< 15%) was higher than that of patients with higher Ki-67 values (>= 15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. Conclusion: DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.