Predictive and prognostic impact of tumour-infiltrating lymphocytes in triple-negative breast cancer treated with neoadjuvant chemotherapy.
Predictive and prognostic impact of tumour-infiltrating lymphocytes in triple-negative breast cancer treated with neoadjuvant chemotherapy.
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肿瘤浸润淋巴细胞在用新辅助化疗治疗的三阴性乳腺癌中的预测性和预后影响。
DOI：
10.3332/ecancer.2017.759
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发表时间：
2017
影响因子：
1.8
通讯作者：
Ruiz-Simón A
中科院分区：
文献类型：
--
作者：
Herrero-Vicent C;Guerrero A;Gavilá J;Gozalbo F;Hernández A;Sandiego S;Algarra MA;Calatrava A;Guillem-Porta V;Ruiz-Simón A
在局部和局部晚期三阴性乳腺癌（TNBC）中，新辅助化疗（NAC）仅在30-35%的患者中诱导pCR。临床和病理因素不足以区分有无pCR机会的患者。肿瘤微环境对肿瘤和肿瘤浸润淋巴细胞（TIL）至关重要。此外，NAC场景是研究TIL水平可能变化的完美设置。使用我们的前瞻性乳腺癌（BC）数据库，我们确定了1998年至2015年间接受NAC治疗的164例TNBC患者，这些患者有足够的诊断活检样本和术后样本。NAC前后的TILs评估采用标准化的方法，对血精-伊红切片进行视觉评估，TILs的数量以十分位数量化。我们根据受试者工作特征（ROC）分析对淋巴细胞为主的乳腺癌进行分类。我们将LPBC分类为浸润bbbb40 %淋巴细胞浸润肿瘤基质。主要终点为TILs对NAC的预测值，次要终点为无病生存期（DFS）。DFS采用Kaplan-Meier法进行分析，组间比较采用长秩检验。使用单因素和多因素Cox模型生成风险比，以确定NAC后TIL和DFS等变量之间的关联。共有164例TNBC患者接受了NAC和手术治疗。主要患者特征列于表1。我们发现蒽环类药物和紫杉烷类药物对NAC的病理完全反应不同；来自58例（88%）pCR的LPBC亚组51与来自106例（9%）pCR的非淋巴细胞显性乳腺癌（LPBC）亚组10，p = 0.001。在中位随访78个月时，LPBC与更好的DFS相关；LPBC和非LPBC患者的3年DFS Kaplan-Meier估计值分别为2%和30%，p = 0.01。单因素和多因素分析证实TIL是DFS的独立预后指标。肿瘤浸润淋巴细胞可常规用于局部晚期TNBC，如蒽环类和紫杉烷类生物标志物治疗，可以区分不同的两个亚组：LPBC患者对NAC pCR的反应非常高，达到88%，而非LPBC患者仅达到9%。此外，非LPBC患者的预后比LPBC患者差。这一数据验证了TIL的预测和预后价值。
In locally and locally advanced triple-negative breast cancer (TNBC), neoadjuvant chemotherapy (NAC) only induces a pCR in 30–35% of patients. Clinical and pathological factors are not enough to distinguish the patients who have no chance of a pCR or not. The tumour microenvironment is critical for cancer and tumour-infiltrating lymphocytes (TIL). Moreover, the NAC scenario is the perfect setting to study possible changes in TIL levels. Using our prospective maintained breast cancer (BC) database, we identified 164 TNBC patients treated with NAC between 1998 and 2015 with enough samples of diagnostic biopsy and after surgery. Evaluation of TILs before and after NAC followed a standardised methodology for visual assessment on haematoxylin–eosin sections and the amounts of TILs were quantitated in deciles. We categorised lymphocyte-predominant breast cancer cutoff according to a receiver operating characteristic (ROC) analysis. We categorised LPBC as involving > 40% lymphocytic infiltration tumour stroma. The primary end point was predictive value of TILs to NAC, and the secondary end point was disease-free survival (DFS). DFS was analysed using the Kaplan–Meier method and the groups were compared with a long-rank test. Univariate and multivariate Cox models were used to generate hazard ratios for determining associations between variables such as TIL after NAC and DFS. A total of 164 TNBC patients were treated with NAC and surgery. The main patients’ characteristics are listed in Table 1. We identify different pathological complete response to anthracycline and taxane-based NAC; LPBC subgroup 51 from 58 patients (88%) pCR versus non- lymphocyte-predominant breast cancer (LPBC) subgroup 10 from 106 (9%) pCR, p = 0.001. At a median follow-up of 78 months, LPBC was associated with better DFS; the three-year Kaplan–Meier estimates for DFS were 2% and 30 % for patients with LPBC and non-LPBC, respectively, p = 0.01. Univariate and multivariate analysis confirmed TIL to be an independent prognostic marker of DFS. Tumour-infiltrating lymphocytes could be routinely used in locally advanced TNBC treated with anthracycline and taxane, such as biomarker, to be enabled the identification of different two subgroups: LPBC patients have a very high response to NAC pCR 88%, meanwhile non-LPBC patients only achieve 9%. Moreover, non-LPBC patients have a worse prognosis than LPBC patients. This data verified the predictive and prognostic value of TIL.