Abstract P4-02-04: Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group

Abstract

Abstract Background: Tumor infiltrating lymphocytes (TILs) are associated with an improved outcome in triple negative and HER2 breast cancers. Conversely, a recent pioneer study showed that TILs in infiltrating lobular carcinoma (ILC) were associated with a worse prognosis. We aimed at assessing the prognostic impact of TILs in a large cohort of primary surgically treated ILC with a long follow-up in a single institution. Methods: We retrospectively reviewed 459 ILC treated at the Curie Institute between 2005 and 2008. Clinico-pathological patients' characteristics were collected and all archived tumor slides were centrally reviewed for TILs quantification. We analyzed stromal TILs scored as a continuous variable. Cox analyses were performed for relapse free survival (RFS) and for overall survival (OS), and chi-square and Fisher test were performed to evaluate the correlation between TILs and other clinico-pathological variables. For statistical analyses, presence or absence of TILs was considered. Results: Patients had a mean age of 60.3 years and a median follow-up of 8.8 years, during which 74 local and/or distant relapse events occurred, among which 37 deaths due to the disease. The presence of TILs were significantly associated with greater tumor size (pT), positive nodal status (pN), molecular class (HER2 amplified), and specific morphological nuclear features such as high nuclear grade, multinucleation, macronucleoli and high Nottingham Prognostic Index class. Presence of intra-tumoral lymphocytes is significantly associated with a worse RFS (HR: 2.07 p=0.003) and OS (HR: 4.58 p<0.001) in a multivariate analysis, independently of chemotherapy. Relapse Free Survival TILs% (IC 95%)% (IC 95%)No95.3 (92.5-98.2)89.0 (84.3-94.0)Yes89.3 (85.1-93.6)74.0 (67.5-81-1) Overall Survival OS at 5 yearsOS at 10 yearsTILs% (IC 95%)% (IC 95%)No99.5 (97.8-100)95.8 (92.3-99.4)Yes95.3 (92.3-98.1)83.5 (77.8-89.7) Conclusion: TILs are an independent prognostic factor associated with a poor outcome in ILC that are easy to assess on diagnostic biopsies. In order to elucidate the role of TILs in ILC, we will further characterize the immune infiltrate and integrate these results with DNA, RNA and protein analyses of the same carcinomas, in order to gain insight into their molecular features and to facilitate the identification of new therapeutic strategies for these ILC with TILs. Citation Format: Tille J-C, Saint Martin C, Fuhrmann L, De Koning L, Reyal F, Piccart M, Kirova Y, Cottu P, Carton M, Vincent Salomon A. Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-04.