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. 2011 Jul 26;105(3):366-71.
doi: 10.1038/bjc.2011.261. Epub 2011 Jul 12.

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

S Ladoire  1 , L Arnould, G Mignot, L Apetoh, C Rébé, F Martin, P Fumoleau, B Coudert, F Ghiringhelli
Affiliations

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

S Ladoire et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
(A) Haematoxylin–eosin–safran labelling of an HER2-overexpressing breast cancer. White arrows indicate tumour islets and the black arrow the paratumoral lymphoid structure (Magnification × 10). Immunohistochemical T-bet staining of paraffin-embedded breast cancer overexpressing HER2. (B) Representative tumour with lymphoid structure devoid of T-bet+ lymphocyte infiltration. (C) Representative tumour with lymphoid structure with T-bet+ lymphocyte infiltration. White arrows show tumour islets (magnification × 10). A detail of lymphoid infiltrate is shown on × 40 magnification.
Figure 2
Figure 2
Presence of T-bet+ T cells in peritumoral lymphoid structure predicts better RFS in patients treated with neoadjuvant taxanes–trastuzumab-based neoadjuvant chemotherapy. Kaplan–Meier curves for RFS stratified according to the presence or absence of T-bet+ T cells after neoadjuvant chemotherapy in (A) patients treated with anthracyclines, (B) patients treated with taxanes–trastuzumab. P-values were calculated using the log-rank test.
See this image and copyright information in PMC

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