Survivin, Ki-67 and tumor grade as predictors of response to docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer

The response rates to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) may vary and the risks may outweigh the benefits in poorly selected patients. This study investigated whether survivin expression, high-level Ki-67 expression, estrogen-receptor (ER) tumor status and high tumor grade are able to predict response to docetaxel-based NAC in LABC patients, in order to perform breast-conserving surgery. In this study, 68 patients (IIb-IIIb) completed 4-6 cycles of TAC (75 mg/m2 docetaxel, 60 mg/m2 pirarubicin and 500 mg/m2 cyclophosphamide, administered every 3 weeks). Tumor samples were obtained prior to chemotherapy. The response to chemotherapy was quantified clinically and pathologically and the histological and molecular tumor characteristics were determined. Association with response was assessed for all the parameters and the patients underwent breast-conserving surgery or radical mastectomy accordingly. A clinical complete response was observed in 21 (31%) and a partial response in 37 (54%) of the 68 patients. Thus, the overall clinical response rate (ORR) was 85%. A pathological complete response (pCR) was observed in 14 (20%) of the 68 patients and 37 patients (54%) underwent breast-conserving surgery. In the univariate analysis, survivin expression, high-level Ki-67 expression and high tumor grade (grade III) were significantly associated with ORR (P=0.007, 0.024 and 0.047, respectively). Survivin expression and high-level Ki-67 expression were significantly associated with pCR (P=0.029 and 0.048, respectively). In the multivariate analysis, survivin expression (P=0.030) and tumor grade (P=0.036), but not high-level Ki-67 and ER expression, were significantly associated with ORR and none of these factors was significantly associated with pCR. In conclusion, expression of survivin and high tumor grade were of predictive value for ORR to docetaxel-based NAC in LABC patients, leading to more patients successfully undergoing breast conserving-surgery. Immunohistochemistry of survivin and the Elston and Ellis criteria of tumor grade may provide a widely applicable, cost-effective method of patient selection for NAC.