Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
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DOI：
10.1093/annonc/mdu112
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发表时间：
2014-08-01
影响因子：
50.5
通讯作者：
Sotiriou, C.
中科院分区：
文献类型：
--
作者：
Loi, S.;Michiels, S.;Sotiriou, C.
背景资料：我们之前已经使用来自大型临床试验队列的肿瘤样本显示了肿瘤浸润淋巴细胞（TIL）在新诊断的三阴性乳腺癌（TNBC）中的预后重要性。在这项研究中，我们的目的是验证这些发现，并探讨与曲妥珠单抗的好处在HER 2-overexpressing disease（HER 2+）.Patients和methods：一个前瞻性回顾性研究进行了使用FinHER辅助，III期试验，招募1010早期BC患者，其中778人是HER 2-nonamplified样本。HER 2+患者（n = 232）随机接受9周曲妥珠单抗治疗或不接受曲妥珠单抗治疗。两名病理学家在935（92.6%）个可用切片中独立定量基质TIL。考克斯回归模型研究了主要终点无远处疾病生存期（DDFS）和与曲妥珠单抗的相互作用。结果：与我们以前的研究结果一致，在TNBC（n = 134）中，TILs每增加10%与TNBC的远处复发显著相关，对于DDFS，经临床病理因素校正的风险比为0.77; 95%置信区间（CI）0.61-0.98，P=0.02。在HER 2 + BC（n = 209）中，淋巴细胞浸润每增加10%与随机分配至曲妥珠单抗组的患者的远端复发率降低显著相关（DDFS P相互作用=0.025）。结论：诊断时存在的较高水平的TIL与原发性TNBC的远端复发率降低显著相关。这些结果证实了我们以前的数据，并进一步支持TIL应被认为是这种BC亚型的一个强有力的预后因素。我们还首次报告了更高水平的TIL与HER 2+疾病中曲妥珠单抗获益增加之间的相关性。需要进一步研究为什么一些TN和HER 2 + BC可以或不能产生宿主抗肿瘤免疫应答以及曲妥珠单抗如何有利地改变免疫微环境。
Background: We have previously shown the prognostic importance of tumor-infiltrating lymphocytes (TILs) in newly diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+).Patients and methods: A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-nonamplified. Those with HER2+ disease (n = 232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92.6%) available slides. The primary end point of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models.Results: Confirming our previous findings, in TNBC (n = 134) each 10% increase in TILs was significantly associated with decreased distant recurrence in TNBC; for DDFS the hazard ratio adjusted for clinicopathological factors: 0.77; 95% confidence interval (CI) 0.61-0.98, P=0.02. In HER2+ BC(n = 209), each 10% increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS Pinteraction=0.025).Conclusions: Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. These results confirm our previous data and further support that TILs should be considered as a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host antitumor immune response and how trastuzumab can favorably alter the immunemicroenvironment is warranted.