Abstract 1412: Prediction of the treatment response to eribulin chemotherapy in breast cancer using tumor-infiltrating lymphocytes (TILs)
Authors: Shinichiro Kashiwagi , Asano Yuka , Goto Wataru , Kurata Kento , Morisaki Tamami , Noda Satoru , Takashima Tsutomu , Onoda Naoyoshi , Tanaka Sayaka , Ohsawa Masahiko , Ohira Masaichi , Hirakawa Kosei 
Published: July 2016

Abstract
Background: Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.
Materials and Methods: TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. The area of in situ carcinoma and crush artifacts were not included. Proportional scores were defined as 3, 2, 1, and 0 if the area of stroma with lymphoplasmacytic infiltration around invasive tumor cell nests was &gt; 50%, &gt; 10 - 50%, ≤ 10%, and absent, respectively. TILs were considered positive when scores were ≥ 2, and negative when scores were 1 and 0.
Results: Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a univariate analysis of recurrence in TNBC patients, being in the high TILs group was a factor for a good outcome (p = 0.047, HR = 0.260). In a multivariate analysis, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).
Conclusions: The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.
Citation Format: Kashiwagi Shinichiro, Yuka Asano, Wataru Goto, Kento Kurata, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Sayaka Tanaka, Masahiko Ohsawa, Masaichi Ohira, Kosei Hirakawa. Prediction of the treatment response to eribulin chemotherapy in breast cancer using tumor-infiltrating lymphocytes (TILs). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1412.