Clinical significance of Smac and survivin expression in breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy

The second mitochondria-derived activator of caspases (Smac), an antagonist of the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro. Survivin, an IAP family member, mediates cancer cell survival and chemoresistance. The present study investigated the correlation between Smac and survivin expression in primary breast cancer, and the sensitivity to anthracycline during neoadjuvant chemotherapy (NAC). Pre-treatment biopsies and post-anthracycline treatment tumor sections were analyzed from 98 cases. Biomarker expression was evaluated by immunohistochemistry in tumor samples from clinical stage II and III anthracycline-based NAC-treated breast cancer. A univariate analysis indicated that the estrogen receptor (ER), Smac and survivin were significantly predictive of a pathological complete response (pCR) (P=0.004, 0.001 and 0.037, respectively) in pre-chemotherapy samples. ER, Smac and survivin expression was also significant for pCR on the multivariate analysis (P=0.001, 0.031 and 0.012, respectively). An inverse association was identified between survivin and Smac expression (r=-0.217, P=0.032; and r=-0.335, P=0.003, respectively) prior to and following NAC. The patients with low survivin expression or high Smac expression had significantly longer disease-free survival (DFS; P=0.012 and P=0.020, respectively) and overall survival (OS; P=0.01 and P=0.033, respectively) compared with the patients with high survivin or low Smac expression. Cox regression analyses demonstrated that survivin, Smac and clinical stage were independent predictors for DFS and OS. The present study indicated the significance of Smac and survivin in determining the breast cancer response to anthracycline-based chemotherapy, and may permit further stratifying of pre-chemotherapy patients to undertake more tailored treatments.