Breast Cancer Research (Dec 2019)

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 Marmé,
  • Christian Schem,
  • Elmar Stickeler,
  • Beyhan Ataseven,
  • Jens Huober,
  • Gunter von Minckwitz,
  • Barbara Seliger,
  • Carsten Denkert,
  • Sibylle Loibl

DOI
https://doi.org/10.1186/s13058-019-1231-z
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 9

Abstract

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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.

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