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

Bruno Valentin Sinn, Karsten E Weber, Wolfgang Daniel Schmitt, Peter A Fasching, William Fraser Symmans, Jens-Uwe Blohmer, Thomas Karn, Eliane Tabea Taube, Frederick Klauschen, Frederik Marme, Christian Schem, Elmar Stickeler, Beyhan Ataseven, Jens Huober, Gunter Von Minckwitz, Barbara Seliger, Carsten Denkert & Sibylle Loibl

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.
   
citation Sinn B V, Weber K E, Schmitt W D, Fasching P A, Symmans W F, Blohmer J U, Karn T, Taube E T, Klauschen F, Marme F, Schem C, Stickeler E, Ataseven B, Huober J, von Minckwitz G, Seliger B, Denkert C, Loibl S. Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy. Breast Cancer Res 2019; 21:142.
   
type journal paper/review (English)
date of publishing 11-12-2019
journal title Breast Cancer Res (21/1)
ISSN electronic 1465-542X
pages 142
PubMed 31829264
DOI 10.1186/s13058-019-1231-z
contact Jens Huober