Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers
Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers
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DOI：
10.1200/jco.18.01010
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发表时间：
2019-03-01
影响因子：
45.3
通讯作者：
Michiels, Stefan
中科院分区：
文献类型：
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作者：
Loi, Sherene;Drubay, Damien;Michiels, Stefan
目的本研究的目的是对研究肿瘤浸润淋巴细胞（TIL）在早期三阴性乳腺癌（TNBC）中的预后价值的研究进行汇总分析。方法参与的研究评估了以蒽环类药物治疗的早期TNBC患者诊断样本中以相同方式定量的基质定位TIL（sTIL）浸润百分比。有或没有紫杉烷类的化疗。按试验分层的考克斯比例风险回归模型被用于浸润性无病生存期（iDFS;主要终点），无远处疾病生存期（D-DFS），和总生存期（OS），拟合sTILs作为一个连续变量调整临床病理factors.ResultsWe收集了来自9项研究的2,148例患者的个体数据。平均年龄为50岁（范围，22至85岁），33%的患者淋巴结阴性。sTILs的平均值为23%（标准差为20%），77%的患者有1%或更多的sTILs。年龄越大（P = 0.001），肿瘤越大（P = 0.01），淋巴结受累越多（P = 0.02），组织学分级越低（P = 0.001），sTILs显著降低。共观察到736例iDFS和548例D-DFS事件以及533例死亡。在多变量模型中，sTILs为所有终点增加了显著的独立预后信息（似然比（2），48.9 iDFS; P <0.001;（2），55.8 D-DFS; P <0.001;（2），48.5 OS; P <0.001）。sTILs每增加10%对应的iDFS风险比为0.87（95% CI，0.83 - 0.91）iDFS，0.83（95% CI，0.79 - 0.88），D-DFS和0.84（95% CI，0.79至0.89）。在sTILs 30%的淋巴结阴性患者中，3年iDFS为92%（95% CI，89%至98%），D-DFS为97%（95% CI，95%至99%），OS为99%（95%可信区间，97%至100%）。结论该汇总数据分析证实了sTILs在早期乳腺癌中的强预后作用。在辅助化疗后，具有高sTIL的患者的TNBC分期和极好的存活率，并且支持将sTIL整合到TNBC患者的临床病理预后模型中。该模型可在www.tilsinbreastcancer.org上找到。
PurposeThe aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC).MethodsParticipating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors.ResultsWe collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age (P = .001), larger tumor size (P = .01), more nodal involvement (P = .02), and lower histologic grade (P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio (2), 48.9 iDFS; P < .001; (2), 55.8 D-DFS; P < .001; (2), 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%).ConclusionThis pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org.