title: 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.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300RC, Leiden, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Engels
authors.forename: A
authors.initials: A
authors.lastname: Charehbili
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: E
authors.initials: E
authors.lastname: Bastiaannet
authors.forename: A
authors.initials: A
authors.lastname: Sajet
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.forename: E A
authors.initials: EA
authors.lastname: van Vliet
authors.forename: R L P
authors.initials: RL
authors.lastname: van Vlierberghe
authors.forename: V T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D059951:HLA-G Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017698:Postmenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013629:Tamoxifen / Q000008:administration & dosage; D000097625:HLA-E Antigens
chemical_list: D000730:Androstadienes; D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000097625:HLA-E Antigens; C418974:FOXP3 protein, human; C056516:exemestane