Abstract P1-07-01: HLA class I expression is associated with tumor-infiltrating lymphocytes and response and survival after neoadjuvant chemotherapy in hormone receptor-positive, HER2-negative breast cancer
Authors: BV Sinn, K Weber, C Denkert, PA Fasching, WD Schmitt, K Thomas, B Ingold-Heppner, M van Mackelenbergh, WF Symmans, F Marmé, E Taube, V Müller, CA Kunze, C Schem, BM Pfitzner, E Stickeler, G von Minckwitz, S Loibl
Journal: Cancer Research (2018)

Abstract Background: Interactions between cancer cells and the host immune system influence tumor biology, response to therapy and patient survival and their modulation offers promising new approaches for cancer therapy. The downregulation or loss of HLA class I expression in breast cancer cells might be an effective mechanism to evade the recognition by the immune system facilitating malignant behavior. Aim: To evaluate the association of tumor-infiltrating lymphocytes (TILs) with HLA class I expression and its theranostic value for therapy response and survival after neoadjuvant chemotherapy. Methods: HLA class I expression was evaluated by immunohistochemistry in a cohort of 732 pre-therapeutic core biopsies from breast cancer patients treated within the neoadjuvant GeparTrio trial. Patients received anthracycline- and taxane-based neoadjuvant therapy and adjuvant endocrine treatment if hormone receptor-positive (HR+). A publicly available microarray dataset of pre-therapeutic core biopsies from 508 breast cancer patients that received neoadjuvant chemotherapy and endocrine treatment if HR+ was used for validation of the results. The association of HLA class I expression with predefined genomic signatures for immune cell populations was evaluated in publicly available data from the cancer genome atlas. Results: HLA class I expression was associated with TILs (p &amp;lt; 0.001) and was predictive of better response to neoadjuvant chemotherapy in the subgroup of patients with HR+/HER2- breast cancer (14 % in tumors with high HLA vs. 7 % in tumors with low HLA, p = 0.029). Interestingly, high HLA was also predictive for shorter progression-free survival in univariate analysis (HR 1.590, 95 % CI 1.062—2.380; p = 0.024) and after adjustment to clinical and pathological parameters (HR 1.701, 95 % CI 1.105—2.618; p = 0.016). The results could be validated in the independent microarray-based dataset (HR 1.521, 95% CI 1.088 – 2.129; p = 0.0142). HLA class I was not associated with therapy response or survival in hormone receptor-negative breast cancer. HLA class I was associated with a predefined signature for T-cells and cytotoxic T- cells in the cancer genome atlas dataset (rho = 0.546). Conclusion: HLA class I expression is associated with better response but shorter progression-free survival in HR+/HER2- breast cancer following neoadjuvant chemotherapy. The underlying mechanisms warrant further investigation. Citation Format: Sinn BV, Weber K, Denkert C, Fasching PA, Schmitt WD, Thomas K, Ingold-Heppner B, van Mackelenbergh M, Symmans WF, Marmé F, Taube E, Müller V, Kunze CA, Schem C, Pfitzner BM, Stickeler E, von Minckwitz G, Loibl S. HLA class I expression is associated with tumor-infiltrating lymphocytes and response and survival after neoadjuvant chemotherapy in hormone receptor-positive, HER2-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-01.