T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival

BACKGROUND: In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival. METHODS: In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS). RESULTS: Fifty-eight patients have been treated with trastuzumab-taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab-taxane (P 0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P = 0.011) only in patients treated with trastuzumab-taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P = 0.04). CONCLUSION: These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab-taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma. British Journal of Cancer (2011) 105, 366-371. doi:10.1038/bjc.2011.261 www.bjcancer.com Published online 12 July 2011 (C) 2011 Cancer Research UK