Changes of Tumor-infiltrating Lymphocytes in Breast Cancer after Neoadjuvant Chemotherapy

ABSTRACT

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study, whether changes in tumor infiltrating lymphocytes take place after neoadjuvant chemotherapy, and if these correlate with the response to treatment in breast cancer were analyzed. METHODS: Neoadjuvant chemotherapy (Adriamycin: 50 mg/m2 +docetaxel: 75 mg/m2, q3wks, 3 treatments) was followed by definitive surgical management. Histological sections from the pre-treatment core-needle biopsy and post-treatment surgical specimens of 17 patients were analyzed for the extent of lymphocytes infiltration. Infiltrated lymphocytes have been recognized as tumor-infiltrating lymphocytes (TILs; lymphocytes present within tumor cell nests). The modified Black's scoring system was used for grading the extent of lymphocytes infiltration, with immunohistochemical (IHC) staining used to characterize the TILs. RESULTS: Pre-treatment lymphocytic infiltrates within the tumor were minimal in the majority of patients, and showed no relationship with the response. A marked increase of TILs after chemotherapeutic treatment was noted in patients according to the following response; complete response: 4/4 (100%), partial response: 2/6 (33.3%), stable disease: 0/7 (0%) (P=0.004). Histological sections stained with IHC staining revealed the increased TILs were CD8 positive cytotoxic T-lymphocytes. CONCLUSION: These results suggest that the development of TILs after treatment correlate with the response to neoadjuvant chemotherapy. Despite the limitation of this preliminary study, the extent of TILs change might be used as a predictor for the therapeutic efficacy of neoadjuvant chemotherapy in breast cancer.