Low Foxp3 cells infiltrate is a marker of pathological complete response to neoadjuvant chemotherapy in breast carcinoma

Abstract

21011 Background: T cell infiltration is associated with tumor prognosis in many cancer types. To assess the capacity of neoadjuvant chemotherapy to impact on T cell infiltration in breast cancer, we investigated if pathological complete response (pCR) to neoadjuvant chemotherapy correlated with T cell infiltration Methods: CD3, CD8 and Foxp3 positive cells were detected by immunohistochemistry in a series of 56 breast cancer patients treated by neoadjuvant chemotherapy. Infiltrates were analysed before and after the end of the treatment. Cytotoxic cells were stained using anti-Granzyme b and TiA1 antibodies Results: Poor prognosis factors (negative hormonal receptors, high tumor grade and nodal involvement) correlated with a significant higher number of CD3, CD8 and Foxp3 cells infiltrates before chemotherapy. Chemotherapy only induced a decrease in the number of Foxp3 cells (p<0.01) while the level of CD8 and CD3 cells were maintained (p=0.8). pCR were observed in 12 patients who had a drastic decrease of Foxp3 positive cells (mean:1.6±1.4 versus 0.08 ± 0.2; p<0.001) while these cells remained elevated in non responders (mean: 1.5±1 versus 1 ± 1 p=0.2). Furthermore, using a cutoff criterion that combined high CD8 infiltration and no Foxp3 cell infiltration on surgical specimens we could predict pCR with a sensitivity of 75% and a specificity of 93%. Cytotoxic effector cells infiltrate was only enhanced in pCR. In multivariate analysis, only high tumor grade and low Foxp3 cell infiltration on final histological specimens were independent predictors of a pCR (HR (95% CI): 17,7394 (1,1 to 272,5) p=0.04 and 0,0132 (0,0002 to 0,9) p=0.04 respectively). The Kaplan Meier estimate of metastasis-free survival indicated a trend toward higher percentage of metastases-free patients in pCR and combined immunological criterion (Log rank test, p=0.1 and p = 0.12 respectively) Conclusions: These findings indicate that pathological complete response to neoadjuvant chemotherapy is associated with an immunological profile consisting in absence of immunosuppressive Foxp3 cells, presence of high number of CD8 T cells, and an increased number of cytotoxic cells. These results argue for the induction of an antitumor immune response by chemotherapy in this group of patients No significant financial relationships to disclose.