Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy
Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy
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DOI：
10.1016/s1470-2045(17)30904-x
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发表时间：
2018-01-01
期刊：
影响因子：
51.1
通讯作者：
Loibl, Sibylle
中科院分区：
文献类型：
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作者：
Denkert, Carsten;von Minckwitz, Gunter;Loibl, Sibylle
肿瘤浸润淋巴细胞（TIL）可预测三阴性乳腺癌（TNBC）和HER 2阳性乳腺癌对新辅助化疗的反应，但其在管腔型乳腺癌中的作用以及TIL对所有亚型预后的影响尚不清楚。在这里，我们评估了TILs的化疗反应和预后与TNBC患者，HER 2阳性乳腺癌，和管腔HER 2阴性breastcancer.Methods新辅助联合化疗治疗的原发性乳腺癌患者的相关性，包括从6个随机试验德国乳腺癌组。根据国际TIL工作组的指南，通过标准化方法评估了这些研究中3771例患者的治疗前核心活检的基质TIL数量。TIL作为连续参数和在低（肿瘤内基质组织中0-10%免疫细胞）、中等（11-59%）和高TIL（>= 60%）的三个预定义组中进行分析。我们在单变量和多变量统计模型中使用这些数据来评估所有患者中TIL浓度与病理学完全缓解之间的关联，以及来自六个临床试验队列中的五个的2560名患者中TIL的量与无病生存期和总生存期之间的关联。759例低TIL患者中有45例（6%）达到病理学完全缓解（pCR），435例中等TIL患者中有48例（11%）达到病理学完全缓解，172例高TIL患者中有49例（28%）达到病理学完全缓解。在HER 2阳性亚型中，在605例低TILs患者中的194例（32%）、512例中等TILs患者中的198例（39%）和262例高TILs患者中的127例（48%）中观察到pCR。最后，在TNBC亚型中，260例低TILs患者中有80例（31%）达到pCR，373例中等TILs患者中有117例（31%）达到pCR，273例高TILs患者中有136例（50%）达到pCR（p
Background Tumour-infiltrating lymphocytes (TILs) are predictive for response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, but their role in luminal breast cancer and the effect of TILs on prognosis in all subtypes is less clear. Here, we assessed the relevance of TILs for chemotherapy response and prognosis in patients with TNBC, HER2-positive breast cancer, and luminal-HER2-negative breast cancer.Methods Patients with primary breast cancer who were treated with neoadjuvant combination chemotherapy were included from six randomised trials done by the German Breast Cancer Group. Pretherapeutic core biopsies from 3771 patients included in these studies were assessed for the number of stromal TILs by standardised methods according to the guidelines of the International TIL working group. TILs were analysed both as a continuous parameter and in three predefined groups of low (0-10% immune cells in stromal tissue within the tumour), intermediate (11-59%), and high TILs (>= 60%). We used these data in univariable and multivariable statistical models to assess the association between TIL concentration and pathological complete response in all patients, and between the amount of TILs and disease-free survival and overall survival in 2560 patients from five of the six clinical trial cohorts.Findings In the luminal-HER2-negative breast cancer subtype, a pathological complete response (pCR) was achieved in 45 (6%) of 759 patients with low TILs, 48 (11%) of 435 with intermediate TILs, and 49 (28%) of 172 with high TILs. In the HER2-positive subtype, pCR was observed in 194 (32%) of 605 patients with low TILs, 198 (39%) of 512 with intermediate TILs, and 127 (48%) of 262 with high TILs. Finally, in the TNBC subtype, pCR was achieved in 80 (31%) of 260 patients with low TILs, 117 (31%) of 373 with intermediate TILs, and 136 (50%) of 273 with high TILs (p