|
编者按：肿瘤浸润淋巴细胞（TIL）已被证明可以预测无病生存，并且可以预测早期乳腺癌患者的化疗获益，但是此前尚未对内分泌治疗进行研究。 2018年5月15日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表荷兰莱顿大学、英国伦敦大学癌症研究院、伦敦帝国学院、加拿大安大略癌症研究院的研究报告，对TIL作为早期乳腺癌术后内分泌辅助治疗的生物学预测指标进行了探索。 作者对组间依西美坦研究（IES）236例患者亚组和他莫昔芬与依西美坦辅助治疗多国研究（TEAM）2596例患者的CD8阳性TIL数量进行评定，分析CD8阳性TIL数量与无病生存、无复发生存、总生存的相关性。前者（IES）将他莫昔芬辅助治疗2～3年后的患者随机分配继续服用他莫昔芬或改为依西美坦直至完成5年疗程（他莫昔芬单药 v.s. 他莫昔芬→依西美坦），后者（TEAM）将患者随机分配服用他莫昔芬→依西美坦 v.s. 依西美坦单药。结果发现： 对于IES研究队列患者，他莫昔芬→依西美坦与他莫昔芬单药相比：
对于TEAM研究队列患者，他莫昔芬→依西美坦与依西美坦单药相比：
因此，该研究首次提出将CD8阳性TIL数量作为内分泌治疗的潜在预测指标，其中CD8阳性TIL数量低与依西美坦治疗相关。不过，该指标仅对样本较小的IES研究队列治疗交互影响有显著预测意义，表明有必要进一步验证。 Breast Cancer Res Treat. 2018 May 15. Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer. Erik J. Blok, Charla C. Engels, Geeske Dekker-Ensink, Elma Meershoek-Klein Kranenbarg, Hein Putter, Vincent T. H. B. M. Smit, Gerrit-Jan Liefers, James P. Morden, Judith M. Bliss, R. Charles Coombes, John M. S. Bartlett, Judith R. Kroep, Cornelis J. H. van de Velde, Peter J. K. Kuppen. Leiden University Medical Center, Leiden, The Netherlands; The Institute of Cancer Research, London, UK; Imperial College, London, UK; Ontario Institute for Cancer Research, MaRS Centre, Toronto, Canada. 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. KEYWORDS: Breast cancer; Tumor infiltrating lymphocytes; Endocrine therapy; Exemestane; Tamoxifen DOI: 10.1007/s10549-018-4785-z
|
|
|
