Estrogen receptor (ER), Ki-67, p27Kip1, and histologic grade as predictors of pathologic complete response (pCR) in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC) using fluorouracil, epirubicin, and cyclophosphamide (FEC), taxanes, and trastuzumab.

613 Background: NAC with taxanes and FEC concurrently with trastuzumab is a potent regimen in patients with HER2-positive breast cancer (BC). Several studies revealed high pCR rates in BC patients treated with this regimen; however, predictive factors and a prognostic effect of pCR have been still unclear. In this study, we analyzed several factors including p27Kip1 (cyclin-dependent kinase inhibitor acting as tumor suppressor) for correlation with pCR. We also evaluated differences in recurrence-free survival (RFS) or overall survival (OS) between patients with pCR and non-pCR, and with positive and negative nodes after NAC. Methods: Our study included 129 Japanese women with invasive, HER2-positive BC who received 12 cycles of paclitaxel or 4 cycles of docetaxel followed by 4 cycles of FEC-75 with concomitant trastuzumab for 24 weeks. We analyzed the correlation of pCR (no invasive lesions in the breast) and nodal status after NAC with RFS and OS, and analyzed the baseline expressions of ER, Ki-67, and p27Kip1, and histological grade for correlation with pCR. Positive or high expression was defined by nuclear labeling index: ER ≥10%, p27Kip1 ≥75%, Ki-67 ≥30%. Results: In 129 patients, pCR was found in 85 (66%). Patients with pCR after NAC had significantly better RFS than those without pCR (median follow-up: 41 months). Furthermore, patients with pathologically negative nodes after NAC had significantly better OS than those with pathologically positive nodes. Negative ER (79% vs. 40%), high Ki-67 (72% vs. 47%), low p27Kip1 (71% vs. 50%), and histological grade 3 (70% vs. 39%) were significant predictors of pCR. Conclusions: In patients with HER2-positive BC, this regimen was effective achieving the high pCR rate. pCR and pathologically negative nodes after NAC were predictive of RFS and OS, respectively. The expressions of ER, Ki-67, and p27Kip1, and histological grade at baseline were predictive of pCR. p27Kip1, a new predictor of pCR after NAC needs to be further analyzed.