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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3269-7) contains supplementary material, which is available to authorized users.

Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis

“…Twenty-four articles were excluded because they lacked essential results concerning data extraction. After excluding studies, 23 studies met the criteria for evaluation, comprising 13,100 cases [6, 8–29]. Although references 20 and 27 came from the same authors, the studies evaluated the distinct outcomes of pathological complete response (pCR) and disease-free survival (DFS).…”

Low BMI is correlated with increased TGF‐β and IL‐10 mRNA levels in the peripheral blood of breast cancer patients

“…All enrolled patients were diagnosed with pathological confirmation and had a nutritional evaluation. We excluded patients who had no peripheral blood collection before treatment; metabolic disease, including diabetes and hyperparathyroidism; inflammatory disease; hematological disease; liver disease and renal disease; infection; other tumors; or inflammatory breast disease. Twenty‐one healthy women were enrolled as controls.…”

“…Twenty‐one healthy women were enrolled as controls. We excluded as controls women who had tumors; breast disease; metabolic disease; inflammatory disease; hematological disease; liver disease and renal disease; or infection. This study was approved by the Ethics Committee of Renmin Hospital of Wuhan University.…”

“…The concept of "cancer immunoediting" describes the dual role of the immune system in cancer, by which it not only inhibits carcinogenesis, but also promotes tumor growth (1). The immune system stimulates tumor evasion by the immunosuppressive function of certain immune cells and molecules, which suppress antigen presentation, cell apoptosis, and the function of cytotoxic lymphocytes and natural killer (NK) cells, and promote angiogenesis (2)(3)(4)(5). Forkhead box P31 (Foxp31) T cells, transforming growth factor-b (TGF-b), and interleukin-10 (IL-10) have been shown to have an immunosuppressive effect and promote the development of breast cancer (2,4,6).…”

“…Forkhead box P31 (Foxp31) T cells, transforming growth factor-b (TGF-b), and interleukin-10 (IL-10) have been shown to have an immunosuppressive effect and promote the development of breast cancer (2,4,6). Previous studies demonstrated that Foxp3, TGF-b, and IL-10 are highly expressed in breast cancer tissues and negatively correlated with the prognosis of breast cancer patients (5,(7)(8)(9)(10)(11)(12)(13)(14). In addition, the levels of these factors are increased in the peripheral blood of individuals with breast cancer compared with healthy controls, and are associated with poor survival (15)(16)(17).…”