Foxp3 expression in breast cancer cells: A new predictor of response to anthracycline versus docetaxel in primary breast cancer treated with adjuvant chemotherapy in the phase III trial FNCLCC/PACS-01.

1026 Background: Predictive markers of response to chemotherapy are lacking in breast cancer patients. Preclinical data suggest that breast cancer cells that loose expression of Foxp3 gene develop resistance to anthracyclines but not to taxane. However, only few conflicting clinical data are available. Using Foxp3 labelling we tested the hypothesis that adjuvant chemotherapy incorporating docetaxel confers an overall survival (OS) benefit over anthracyclines in Foxp3-negative tumors while anthracycline and docetaxel are equivalent in Foxp3 expressing tumors. METHODS We obtained breast tumor tissue from patients included in breast cancer adjuvant trial PACS-01. This study compared 3 cycles of anthacycline followed by 3 cycles of docetaxel versus 6 cycles of anthracycline. Tumor sections were labeled with anti Foxp3 antibody using immunochemistry. Foxp3 expression was determined blinded to data. Cox models were used to estimated HR for OS with 95%CI of Foxp3 expression according to chemotherapy adjusted for clinical characteristics (tumor grade, tumor size and number of lymph node involved). RESULTS Foxp3 status was assessable in 1097 patients. The median age was 50 years old. The median follow up was 96 months. 405 tumors were found to express Foxp3 (36.9%). Using multivariate analysis, using patients treated with anthracycline alone and without Foxp3 expression as a control group, we observed that adjuvant regimen incorporating docetaxel was associated with a significant reduction in the risk of death (HR=0.62; 95%CI: 0.43-0.88, p=0.008). By contrast, in patients with tumor expressing Foxp3, regimen with or without docetaxel gave similar benefit, and adjunction of docetaxel did not improve the risk of death compared to patients treated with anthracycline alone (HR=0.62; 95%CI: 0.4-0.97, p=0.035 and HR=0.57; 95%CI: 0.36-0.90, p=0.16 compared to control group). CONCLUSIONS Foxp3 expression by breast tumor cells predicts resistance to anthracycline regimen, and may be used for the selection of patients that benefit from adjunction of docetaxel in adjuvant chemotherapy for localized breast cancer.