Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer.

Autor: Blok EJ; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., Engels CC; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands., Dekker-Ensink G; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands., Meershoek-Klein Kranenbarg E; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands., Putter H; Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands., Smit VTHBM; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Liefers GJ; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands., Morden JP; Clinical Trials & Statistics Unit, The Institute of Cancer Research, London, UK., Bliss JM; Clinical Trials & Statistics Unit, The Institute of Cancer Research, London, UK., Coombes RC; Department of Surgery & Cancer, Imperial College, London, UK., Bartlett JMS; Ontario Institute for Cancer Research, MaRS Centre, Toronto, Canada., Kroep JR; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., van de Velde CJH; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands., Kuppen PJK; Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. p.j.k.kuppen@lumc.nl.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2018 Aug; Vol. 171 (1), pp. 65-74. Date of Electronic Publication: 2018 May 15.
DOI: 10.1007/s10549-018-4785-z
Abstrakt: Purpose: Tumour-infiltrating lymphocytes (TILs) have been shown to be prognostic for disease-free survival and predictive for the benefit of chemotherapy in patients with early breast cancer, but have not been studied for endocrine therapy.
Experimental Design: The number of CD8-positive TILs was assessed in a subcohort of 236 patients in the Intergroup Exemestane Study. AQ After 2-3 years of adjuvant tamoxifen, AQpatients were randomized between the schemes of continuation for 5 years on tamoxifen and switching to exemestane. The numbers of CD8-positive TILs were analysed for correlations with disease-free survival (DFS) and overall survival (OS). A similar analysis was performed on 2596 patients in the TEAM trial who were randomized between the sequential scheme and the exemestane monotherapy.
Results: In the first cohort, patients with low (below median) numbers of CD8-positive TILs had a univariate hazard ratio (HR) for DFS of 0.27 (95% CI 0.13-0.55) in favour of treatment with exemestane, whereas this benefit was not observed in patients with high numbers of CD8-positive TILs (HR 1.34, 95% CI 0.71-2.50, HR for interaction 5.02, p = 0.001). In the second cohort, patients with low numbers of CD8-positive TILs showed a benefit of exemestane treatment on recurrence-free survival (RFS HR 0.67, 95% CI 0.45-0.99), and not with above-median numbers of CD8-positive TILs (HR 0.86, 95% CI 0.59-1.26, HR for interaction 1.29, p = 0.36).
Conclusions: This study is the first to propose the number of CD8-positive TILs as potential predictive markers for endocrine therapy, with the low presence of CD8-positive TILs associated to benefit for exemestane-inclusive therapy. However, treatment-by-marker interactions were only significant in one cohort, indicating the need for further validation.
Databáze: MEDLINE
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