e22073 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. In this context, tumor infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in tissue specimens and in peripheral blood are being tested as two emerging prognostic and predictive factors. We designed a protocol to analyze specifically TILs before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response. Methods: From March 2011 to January 2013, 48 patients (18 HER2+/ 30 HER2-) with T2-4 N0-3 breast carcinoma treated with neoadjuvant chemotherapy in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study protocol. CD3+, CD8+, CD8-16-56+ and Foxp3+ cell infiltrates were detected by immunohistochemistry before and after the end of neoadjuvant chemotherapy in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle of CT to determine the immunophenotype and regulatory cell profile. Cell populations were determined by flow cytometry analysis of whole blood. Results: By January 2013, 35 patients (11 HER2+/ 24 HER2-) were operated. Pathological complete responses (pCR) or near pCR (grade 4/5 Myller and Payne) were attained in 13 patients. pCR was achieved in 63.63% (7 of 11) of tumors overexpressing HER2, but in only a 25% (6 of 24) of HER2-negative tumors. Overall Tregs diminished in the pCR and non pCR groups. Disappearance of Tregs (Black grading system) was more frequent in the pCR group (69.23 vs 54.54%) and HER2+ population (63.63 vs 58.53%), although differences were not statistically significant. CD8+ infiltrates remain stable during treatment. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates with no changes in CD8+ cytotoxic lymphocytes. Changes observed in lymphocytic infiltrates during neoadjuvant treatment indicate that Tregs may represent an interesting therapeutic target in breast carcinoma.
Correlation between peripheral blood inflammatory indicators and pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer patients
