ImportanceThe absolute benefit of chemotherapy for all patients with stage I triple-negative breast cancer (TNBC) is unclear, and biomarkers are not currently available for selecting patients with an excellent outcome for whom neoadjuvant or adjuvant chemotherapy may have negligible benefit. High levels of stromal tumor-infiltrating lymphocytes (sTILs) are associated with favorable survival in TNBC, but data solely in stage I TNBC are lacking.ObjectiveTo examine the outcomes of patients of all ages with stage I TNBC solely and who received neither neoadjuvant nor adjuvant chemotherapy, according to centrally reviewed sTIL levels at prespecified cutoffs.Design, Setting, and ParticipantsThis cohort study used the Netherlands Cancer Registry to identify patients diagnosed with stage I TNBC between January 1, 2005, and December 31, 2015, who were not treated with chemotherapy. Only patients who did not receive neoadjuvant and/or adjuvant chemotherapy were selected. The clinical data were matched with their corresponding pathology data provided by the Dutch Pathology Registry. Data analysis was performed between February and October 2023.Main Outcomes and MeasuresThe primary end point was breast cancer–specific survival (BCSS) at 5, 10, and 15 years for the prespecified sTIL level cutoffs of 30%, 50%, and 75%. Hematoxylin and eosin–stained slides were used for central review of histologic subtype, grade, and lymphovascular invasion. The International Immuno-Oncology Biomarker Working Group guidelines were used to score the sTIL levels; these levels were determined for 1041 patients.ResultsA total of 4511 females with stage I TNBC (mean [SD] age at diagnosis, 64.4 [11.1] years; median follow-up, 11.4 [95% CI, 10.9-11.9] years) were included. Most tumors (952 [91.5%]) were invasive carcinomas of nonspecial histologic subtype. Most patients (548 [52.6%]) had pT1cN0 tumors. Median (range) sTIL level was 5% (1%-99%). A total of 775 patients (74.4%) had sTIL levels below 30%, 266 (25.6%) had 30% or greater, 203 (19.5%) had 50% or greater, and 141 (13.5%) had 75% or greater. Patients with pT1abN0 tumors had a more favorable outcome vs patients with pT1cN0 tumors, with a 10-year BCSS of 92% (95% CI, 89%-94%) vs 86% (95% CI, 82%-89%). In the overall cohort, sTIL levels of at least 30% were associated with better BCSS compared with sTIL levels less than 30% (96% and 87%, respectively; hazard ratio [HR], 0.45; 95% CI, 0.26-0.77). High sTIL levels of 50% or greater were associated with a better outcome than low sTIL levels of less than 50% (HR, 0.27; 95% CI, 0.10-0.74) in patients with pT1C tumors, with a 10-year BCSS of 95% increasing to 98% with sTIL levels of 75% or greater.Conclusions and RelevanceResults of this study showed that patients with stage I TNBC and high level of sTILs who did not receive neoadjuvant or adjuvant chemotherapy had excellent 10-year BCSS. The findings further support the role of sTILs as integral biomarkers in prospective clinical trials of therapy optimization for this patient population.

中文翻译：

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未经化疗的 I 期三阴性乳腺癌患者的肿瘤浸润淋巴细胞


重要性化疗对所有 I 期三阴性乳腺癌 (TNBC) 患者的绝对益处尚不清楚，目前还没有生物标志物可用于选择新辅助或辅助化疗的益处可能微不足道的具有良好预后的患者。高水平的间质肿瘤浸润淋巴细胞 (sTIL) 与 TNBC 的良好生存相关，但缺乏仅 I 期 TNBC 的数据。 目的检查所有年龄段的仅 I 期 TNBC 且既未接受新辅助治疗也未接受辅助治疗的患者的结局设计、设置和参与者这项队列研究使用荷兰癌症登记处来识别 2005 年 1 月 1 日至 2015 年 12 月 31 日期间诊断为 I 期 TNBC 的患者，这些患者未接受过化疗化疗。仅选择未接受新辅助和/或辅助化疗的患者。临床数据与荷兰病理学登记处提供的相应病理数据相匹配。数据分析于 2023 年 2 月至 10 月期间进行。主要结果和测量主要终点是在预先指定的 sTIL 水平截止值 30%、50% 和 75% 下，5 年、10 年和 15 年的乳腺癌特异性生存率 (BCSS) 。苏木精和伊红染色的载玻片用于组织学亚型、分级和淋巴血管侵犯的集中审查。国际免疫肿瘤学生物标志物工作组指南用于对 sTIL 水平进行评分；这些水平是针对 1041 名患者确定的。 结果共有 4511 名 I 期 TNBC 女性（诊断时平均 [SD] 年龄，64.4 [11.1] 岁；中位随访时间，11.4 [95% CI，10.9-11.9] 年）包括。大多数肿瘤（952 [91.5%]）是非特殊组织学亚型的浸润性癌。大多数患者（548 名 [52.6%]）患有 pT1cN0 肿瘤。中位（范围）sTIL 水平为 5% (1%-99%)。共有 775 名患者 (74.4%) 的 sTIL 水平低于 30%，266 名患者 (25.6%) 的 sTIL 水平为 30% 或更高，203 名患者 (19.5%) 的 sTIL 水平为 50% 或更高，141 名患者 (13.5%) 的 sTIL 水平为 75% 或更高。 pT1abN0 肿瘤患者的预后优于 pT1cN0 肿瘤患者，10 年 BCSS 分别为 92%（95% CI，89%-94%）和 86%（95% CI，82%-89%）。在整个队列中，与 sTIL 水平低于 30% 相比，至少 30% 的 sTIL 水平与更好的 BCSS 相关（分别为 96% 和 87%；风险比 [HR]，0.45；95% CI，0.26-0.77） 。对于 pT1C 肿瘤患者，50% 或更高的高 sTIL 水平与低于 50% 的低 sTIL 水平相比，预后更好（HR，0.27；95% CI，0.10-0.74），10 年 BCSS 为 95当 sTIL 水平达到 75% 或更高时，% 增加到 98%。 结论和相关性 这项研究的结果表明，未接受新辅助或辅助化疗的 I 期 TNBC 和高水平 sTIL 患者具有出色的 10 年 BCSS。这些发现进一步支持了 sTIL 作为该患者群体治疗优化的前瞻性临床试验中不可或缺的生物标志物的作用。