Human leucocyte antigen class i in hormone receptor-positive, HER2-negative breast cancer: Association with response and survival after neoadjuvant chemotherapy

Sinn BV, Weber KE, Schmitt WD, Fasching P, Symmans WF, Blohmer JU, Karn T, Taube ET, Klauschen F, Marmé F, Schem C, Stickeler E, Ataseven B, Huober J, Von Minckwitz G, Seliger B, Denkert C, Loibl S (2019)

Publication Type: Journal article

Publication year: 2019

Journal

BREAST CANCER RES BioMed Central

Book Volume: 21

Article Number: 142

Journal Issue: 1

DOI: 10.1186/s13058-019-1231-z

Abstract

Background: Clinical application of cancer immunotherapy requires a better understanding of tumor immunogenicity and the tumor microenvironment. HLA class I molecules present antigens to CD8+ cytotoxic cells. Their loss or downregulation is frequently found in tumors resulting in reduced T cell responses and worse prognosis. Methods: We evaluated HLA class I heavy chain expression by immunohistochemistry in 863 biopsies (GeparTrio trial). Patients received neoadjuvant chemotherapy and adjuvant endocrine treatment if tumors were hormone receptor-positive (HR+). In parallel, the expression of HLA-A was analyzed using a microarray cohort of 320 breast cancer patients from the MD Anderson Cancer Center. We evaluated its association with clinical outcome, tumor-infiltrating lymphocytes (TILs), and immune cell metagenes. Results: In HR+/HER2- breast cancer, HLA class I heavy chain expression was associated with increased TILs and better response to chemotherapy (7% vs. 14% pCR rate, P = 0.029), but worse disease-free survival (hazard ratio (HR) 1.6 (1.1-2.4); P = 0.024). The effect was significant in a multivariate model adjusted for clinical and pathological variables (HR 1.7 (1.1-2.6); P = 0.016) and was confirmed by analysis of HLA-A in a microarray cohort. HLA-A was correlated to most immune cell metagenes. There was no association with response or survival in triple-negative or HER2+ disease. Conclusions: The study confirms the negative prognostic role of lymphocytes in HR+ breast cancer and points at a complex interaction between chemotherapy, endocrine treatment, and tumor immunogenicity. The results point at a subtype-specific and potentially treatment-specific role of tumor-immunological processes in breast cancer with different implications in triple-negative and hormone receptor-positive disease.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) GBG Forschungs GmbH (German Breast Group) DE Germany (DE) University of Texas MD Anderson Cancer Center US United States (USA) (US) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) Kliniken Essen-Mitte DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE)

How to cite

APA:

Sinn, B.V., Weber, K.E., Schmitt, W.D., Fasching, P., Symmans, W.F., Blohmer, J.U.,... Loibl, S. (2019). Human leucocyte antigen class i in hormone receptor-positive, HER2-negative breast cancer: Association with response and survival after neoadjuvant chemotherapy. BREAST CANCER RES , 21(1). https://doi.org/10.1186/s13058-019-1231-z

MLA:

Sinn, Bruno Valentin, et al. "Human leucocyte antigen class i in hormone receptor-positive, HER2-negative breast cancer: Association with response and survival after neoadjuvant chemotherapy." BREAST CANCER RES 21.1 (2019).

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