Use of Ki-67 in residual disease following preoperative chemotherapy to predict of recurrence and death in breast cancer patients.

Background: The achievement of a pathologic complete response (pCR) after preoperative chemotherapy (PCT) is a powerful predictor of long term outcome, while the prognosis in case of less than pCR is heterogeneous. In two independent studies, posttherapy ki67 was a significant predictor of outcome in breast cancer (BC) patients with residual disease after PCT. The aim of the present study was to evaluate the prognostic significance of posttherapy Ki-67 in an independent patient cohort. Methods: Patients with residual disease following PCT and with posttherapy Ki-67 evaluation by IHC were identified by searching the Breast Medical Oncology database. Patient characteristics including clinical stage, hormone receptors and HER2 status, type of chemotherapy and nodal status after PCT were recorded. The 15% cut-off to define high posttherapy Ki-67 was selected from our previous study (Guarneri, Ann Oncol 2009). Survival rates were estimated with the Kaplan-Meier method; hazard ratios (HRs) by Cox model. Results: Ninety-four patients were included. Median age was 48 years. 69% of the patients had clinical stage I-IIB BC. According to the expression of ER, PgR, and HER2, tumors were classified in the following subtypes: hormone receptor positive/HER2 negative (58%), HER2 positive (18%), and triple receptor negative (18%). All the patients received anthracycline-taxane-containing PCT. The mean posttherapy Ki-67 was 27%. In univariate analyses, clinical stage at diagnosis, posttherapy Ki-67 and BC subtypes were significantly associated with disease-free and overall survival. In multivariate analyses, the HRs for relapse were 6.7 in case of clinical stage III (p < 0.001), 2.9 in case of triple negative disease (p = 0.017), and 6.8 in case of high posttherapy Ki-67 (p < 0.001). The HRs for death were 4.4 in case of clinical stage III (p = 0.005), 3.6 in case of triple negative disease (p = 0.004), and 2.7 in case of high posttherapy Ki-67 (p = 0.026). Conclusions: High posttherapy proliferation is confirmed as an independent predictor of disease-free and overall survival in BC patients with residual disease after PCT.