Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer.
Embargo End Date
ICR Authors
Authors
Blok, EJ
Engels, CC
Dekker-Ensink, G
Meershoek-Klein Kranenbarg, E
Putter, H
Smit, VTHBM
Liefers, G-J
Morden, JP
Bliss, JM
Coombes, RC
Bartlett, JMS
Kroep, JR
van de Velde, CJH
Kuppen, PJK
Engels, CC
Dekker-Ensink, G
Meershoek-Klein Kranenbarg, E
Putter, H
Smit, VTHBM
Liefers, G-J
Morden, JP
Bliss, JM
Coombes, RC
Bartlett, JMS
Kroep, JR
van de Velde, CJH
Kuppen, PJK
Document Type
Journal Article
Date
2018-08-01
Date Accepted
2018-04-07
Abstract
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.
Citation
Breast cancer research and treatment, 2018, 171 (1), pp. 65 - 74
Source Title
Publisher
SPRINGER
ISSN
0167-6806
eISSN
1573-7217
Collections
Research Team
Clinical Trials & Statistics Unit