Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
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DOI：
10.1200/jco.2013.55.0491
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发表时间：
2014-09-20
影响因子：
45.3
通讯作者：
Badve, Sunil S.
中科院分区：
文献类型：
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作者：
Adams, Sylvia;Gray, Robert J.;Badve, Sunil S.
目的近年来的研究表明，肿瘤浸润淋巴细胞（TIL）与可手术三阴性乳腺癌（TNBC）的无病生存（DFS）和总生存（OS）有关。我们试图验证TILs在原发性TNBC中的预后影响，在两个辅助III期临床试验进行了东部肿瘤协作组（ECOG）。患者和MethodsFull-face苏木素和伊红染色切片的506肿瘤从ECOG试验E2197和E1199进行了评价，在上皮内（iTILs）和间质室（sTILs）的TILs密度。根据切片的可用性，随机选择E2197和E1199的TNBC患者病例。对于DFS的主要终点，通过拟合研究分层的比例风险模型确定与TIL评分的相关性。次要终点为OS和远端无复发间期（DRFI）。肿瘤标志物预后研究标准的报告建议如下，所有的分析是prespecified.ResultsThe大多数481可评估的癌症有TILs（sTILs，80%; iTILs，15%）。中位随访时间为10.6年，较高的sTIL评分与较好的预后相关; sTIL每增加10%，复发或死亡风险就会降低14%（P = 0.02），远处复发风险降低18%（P = 0.04），死亡风险降低19%（P = 0.01）。多变量分析证实sTILs是一个独立的预后指标DFS，DRFI，和OS.ConclusionIn两个国家的随机临床试验，使用当代辅助化疗，我们证实，间质淋巴细胞浸润构成了一个强大的预后因素在TNBC。评估结局和治疗效果的研究应考虑该参数的分层。(C)2014年美国临床肿瘤学会
PurposeRecent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).Patients and MethodsFull-face hematoxylin and eosin-stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence-free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.ResultsThe majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.ConclusionIn two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter. (C) 2014 by American Society of Clinical Oncology