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.

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.

• Authors: C C Engels, A Charehbili, C J H van de Velde, E Bastiaannet, A Sajet, H Putter, E A van Vliet, R L P van Vlierberghe, V T H B M Smit, J M S Bartlett, C Seynaeve, G J Liefers, P J K Kuppen
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 149 Issue 3 Pg. 587-96 (Feb 2015) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 25616355 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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