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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.

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.

SUBMITTER: Sinn BV

PROVIDER: S-EPMC6907189 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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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.

Sinn Bruno Valentin BV Weber Karsten E KE Schmitt Wolfgang Daniel WD Fasching Peter A PA Symmans William Fraser WF Blohmer Jens-Uwe JU Karn Thomas T Taube Eliane Tabea ET Klauschen Frederick F Marmé Frederik F Schem Christian C Stickeler Elmar E Ataseven Beyhan B Huober Jens J von Minckwitz Gunter G Seliger Barbara B Denkert Carsten C Loibl Sibylle S

Breast cancer research : BCR 20191211 1

<h4>Background</h4>Clinical application of cancer immunotherapy requires a better understanding of tumor immunogenicity and the tumor microenvironment. HLA class I molecules present antigens to CD8<sup>+</sup> cytotoxic cells. Their loss or downregulation is frequently found in tumors resulting in reduced T cell responses and worse prognosis.<h4>Methods</h4>We evaluated HLA class I heavy chain expression by immunohistochemistry in 863 biopsies (GeparTrio trial). Patients received neoadjuvant che ...[more]

PMID: 31829264

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Project description:We reviewed randomized phase II/III trials comparing first- or second-line endocrine therapy as monotherapy or in combination with targeted therapies for treatment of postmenopausal patients with hormone receptor-positive advanced breast cancer. First-line was defined as treatment for endocrine therapy-naïve advanced breast cancer or advanced disease treated with endocrine therapy in the adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for advanced breast cancer following disease progression on endocrine therapy for advanced disease. Publications reporting progression-free survival (PFS)/time to progression (TTP) or overall survival (OS) for FDA-approved agents anastrozole, exemestane, fulvestrant 250 mg, fulvestrant 500 mg, letrozole (0.5 and 2.5 mg), megestrol acetate, and tamoxifen as monotherapy, or in combination with everolimus, palbociclib or ribociclib, were assessed. First-line monotherapy with anastrozole, fulvestrant 500 mg or letrozole 2.5 mg significantly improved PFS/TTP versus comparator endocrine therapy; however, only fulvestrant 500 mg improved OS. For endocrine therapy in combination with targeted therapies, palbociclib plus letrozole 2.5 mg, and ribociclib plus letrozole 2.5 mg significantly improved PFS versus letrozole 2.5 mg alone first-line. For second-line monotherapies, exemestane, fulvestrant 500 mg and letrozole 2.5 mg significantly improved PFS/TTP versus comparator endocrine therapy; only fulvestrant 500 mg and letrozole 2.5 mg improved OS. For second-line combination therapies, everolimus plus exemestane, and palbociclib plus fulvestrant 500 mg, improved PFS versus endocrine therapy alone. In both first- and second-line settings, aromatase inhibitors demonstrated PFS benefits versus comparator endocrine therapy; however, fulvestrant 500 mg was the only endocrine therapy included in our review to show both PFS and OS advantages compared with other endocrine therapies. Targeted agents in combination with endocrine therapy have demonstrated PFS improvements both first- and second-line; OS data are awaited.

Dataset Information

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

Publications

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

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