The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis

Breast Cancer Res Treat. 2015 Feb;149(3):587-96. doi: 10.1007/s10549-015-3269-7. Epub 2015 Jan 24.

Abstract

Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95% CI 0.560-0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95% CI 0.878-2.297; HR low IS 1.657, 95% CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95% CI 1.375-4.495; HR low IS 2.422, 95% CI 1.439-4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95% CI 0.950-2.395; HR low IS 1.848, 95% CI 1.277-2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androstadienes / administration & dosage
  • Biomarkers, Tumor / immunology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Female
  • Forkhead Transcription Factors / immunology
  • HLA-E Antigens
  • HLA-G Antigens / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunophenotyping*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Postmenopause
  • Prognosis
  • Receptors, Estrogen / genetics
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Tamoxifen / administration & dosage

Substances

  • Androstadienes
  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Receptors, Estrogen
  • Tamoxifen
  • exemestane