肿瘤浸润淋巴细胞改善了三阴性乳腺癌患者接受无蒽环类药物新辅助化疗的结局。
Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy.
机构信息
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
出版信息
Clin Cancer Res. 2024 May 15;30(10):2160-2169. doi: 10.1158/1078-0432.CCR-24-0106.
PURPOSE
Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.
EXPERIMENTAL DESIGN
This is a pooled analysis of two studies where patients with stage I (T>1 cm)-III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC. sTILs were evaluated centrally on pre-treatment hematoxylin and eosin slides using standard criteria. Cox regression analysis was used to examine the effect of variables on event-free survival (EFS) and overall survival (OS).
RESULTS
Among 474 patients, 44% had node-positive disease. Median sTILs were 5% (range, 1%-95%), and 32% of patients had ≥30% sTILs. pCR rate was 51%. On multivariable analysis, T stage (OR, 2.08; P = 0.007), nodal status (OR, 1.64; P = 0.035), and sTILs (OR, 1.10; P = 0.011) were associated with pCR. On multivariate analysis, nodal status (HR, 0.46; P = 0.008), pCR (HR, 0.20; P < 0.001), and sTILs (HR, 0.95; P = 0.049) were associated with OS. At 30% cut-point, sTILs stratified outcomes in stage III disease, with 5-year OS 86% versus 57% in ≥30% versus <30% sTILs (HR, 0.29; P = 0.014), and numeric trend in stage II, with 5-year OS 93% versus 89% in ≥30% versus <30% sTILs (HR, 0.55; P = 0.179). Among stage II-III patients with pCR, EFS was better in those with ≥30% sTILs (HR, 0.16; P, 0.047).
CONCLUSIONS
sTILs density was an independent predictor of OS beyond clinicopathologic features and pathologic response in patients with TNBC treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond tumor-node-metastasis (TNM) stage and pathologic response. These findings highlight the role of sTILs in patient selection and stratification for neo/adjuvant escalation and de-escalation strategies.
目的
在基于蒽环类药物化疗的情况下，基质肿瘤浸润淋巴细胞（sTIL）与三阴性乳腺癌（TNBC）的病理完全缓解（pCR）和长期结局相关。sTIL 在蒽环类药物免费新辅助化疗（NAC）中提供的预后信息之外，对改善结局的影响尚不清楚。
实验设计
这是两项研究的汇总分析，其中 I 期（T>1cm）-III 期 TNBC 患者接受卡铂（AUC 6）加多西紫杉醇（75mg/m2；CbD）NAC。使用标准标准在预处理苏木精和伊红载玻片上对 sTIL 进行中心评估。使用 Cox 回归分析检查变量对无事件生存（EFS）和总生存（OS）的影响。
结果
在 474 名患者中，44%有淋巴结阳性疾病。中位 sTILs 为 5%（范围 1%-95%），32%的患者 sTILs≥30%。pCR 率为 51%。多变量分析显示，T 期（OR，2.08；P=0.007）、淋巴结状态（OR，1.64；P=0.035）和 sTILs（OR，1.10；P=0.011）与 pCR 相关。多变量分析显示，淋巴结状态（HR，0.46；P=0.008）、pCR（HR，0.20；P<0.001）和 sTILs（HR，0.95；P=0.049）与 OS 相关。在 30%的切点处，sTILs 在 III 期疾病中分层了结局，≥30%与<30% sTILs 的 5 年 OS 分别为 86%和 57%（HR，0.29；P=0.014），在 II 期有数值趋势，≥30%与<30% sTILs 的 5 年 OS 分别为 93%和 89%（HR，0.55；P=0.179）。在接受蒽环类药物免费 CbD 化疗的 TNBC 患者中，pCR 患者中 sTILs 密度与 EFS 更好（HR，0.16；P，0.047）。
结论
sTILs 密度是三阴性乳腺癌患者接受蒽环类药物免费 CbD 化疗后，除临床病理特征和病理反应外，OS 的独立预测因子。值得注意的是，sTILs 密度在肿瘤-淋巴结-转移（TNM）分期和病理反应之外分层了结局。这些发现强调了 sTILs 在新辅助/辅助升级和降级策略的患者选择和分层中的作用。
Zotero 插件