BACKGROUND The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy. PATIENTS AND METHODS Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization. RESULTS TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71-0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68-0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy. CONCLUSION In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.

中文翻译：

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III期乳腺癌患者的肿瘤浸润淋巴细胞（TILs）和BRCA样状态随机分配到辅助化疗和常规化疗。

背景技术肿瘤浸润淋巴细胞（TILs）的预后价值因乳腺癌（BC）亚型而异。这项研究的目的是在BRCA1 / 2样表型的背景下评估BC期III的TIL，并与强化铂类化学疗法的预后和获益相关。患者与方法患者参加了1993年至1999年间在BC期III期进行的辅助性强化铂类化疗与常规蒽环类化疗的随机对照试验。在这些人类表皮生长因子受体2（HER2）阴性肿瘤中，根据国际指南对基质TIL进行了评分。使用比较基因组杂交技术确定BRCA谱。结果在248 BCs中评估了TIL水平。高TIL与三阴性BC（TNBC）相关。与非BRCA样肿瘤相比，BRCA样肿瘤具有更高的TIL（中位TIL为20％对10％，p <0.01）。与BRCA2类肿瘤相比，BRCA1类肿瘤的TIL水平更高（中位TIL为20％对10％，p <0.001）。这些相关性在雌激素（ER）阳性亚组中仍然很显着，但在TNBC亚组中则没有。在这个BC期III期队列中，高TIL水平与良好的预后相关（每10％的TIL，无复发生存（RFS）：多元风险比（HR）0.82、95％的置信区间（CI）0.71-0.94，p = 0.01；总生存期（OS）：多变量HR 0.80，95％CI 0.68-0.94，p = 0.01）。TIL与强化铂类化疗获益之间无显着相互作用。结论在这个高危乳腺癌人群中，高TIL与TNBC和BRCA1样状态相关。在ER阳性亚组中，与BRCA2样肿瘤相比，BRCA1样肿瘤的TIL水平更高。调整临床特征后，TIL与BC期III期患者的更有利结局显着相关。