激素受体阳性/HER2 阴性乳腺癌中 TIL（肿瘤浸润淋巴细胞）与 Oncotype DX 雌激素受体、孕激素受体和人表皮生长因子受体 2 单基因评分的关联

英文原题：Association between tumor-infiltrating lymphocytes and oncotype DX estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 single gene scores in hormone receptor-positive/HER2-negative breast cancer.

查看英文原题

Association between tumor-infiltrating lymphocytes and oncotype DX estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 single gene scores in hormone receptor-positive/HER2-negative breast cancer.

PubMed 2026/01/27（内容时间） Front Oncol Q2 · IF 3.4（JCR 2025）

靶点：HER2 乳腺癌地区：日本

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研究概要

在 HR+/HER2- 乳腺癌中，HER2 mRNA 表达较低的肿瘤表现出更高的淋巴细胞浸润，提示存在一个独特的免疫活跃亚群。

中文摘要

**引言：**TIL（肿瘤浸润淋巴细胞）已是三阴性和HER2阳性乳腺癌的成熟生物标志物，但其在激素受体阳性、HER2阴性（HR+/HER2−）乳腺癌中的临床意义尚不明确。本研究考察HR+/HER2−乳腺癌中TIL与Oncotype DX雌激素受体（ER）、孕激素受体（PgR）和HER2单基因评分的关系。 **方法：**回顾性分析2022年1月至2024年10月在埼玉医科大学国际医疗中心接受手术及Oncotype DX检测的260例HR+/HER2−乳腺癌患者。依据2014年国际TIL工作组指南，在苏木精—伊红染色切片上评估TIL，以10%为高TIL界值。通过包括逻辑回归在内的统计分析，考察TIL与临床病理因素及Oncotype DX单基因评分的关联；另分析癌症基因组图谱（TCGA）公开数据进行验证。 **结果：**32例（12.3%）患者TIL较高。与低TIL肿瘤相比，高TIL肿瘤Oncotype DX单基因ER表达（9.8±1.9比10.5±1.3，P<0.01）、PgR表达（6.3±2.2比7.4±1.8，P<0.01）及HER2表达（8.5±0.7比9.2±0.6，P<0.001）均显著较低。多变量分析确定淋巴结阴性（OR=0.266；P=0.0159）及较低HER2单基因表达（OR=0.293；P=0.00144）为高TIL的独立预测因素。TCGA分析证实HER2 mRNA表达较低与趋化因子基因表达升高相关。 **讨论：**HR+/HER2−乳腺癌中，HER2 mRNA表达较低的肿瘤淋巴细胞浸润较高，提示存在一种独特的免疫活跃亚群。Oncotype DX单基因评分，尤其是HER2评分，可能提供复发风险预测以外的信息，并有助识别可能从免疫调节治疗策略获益的患者。

展开英文摘要原文

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) are established biomarkers in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancers; however, their clinical significance in hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer remains unclear. This study aimed to investigate the association between TILs and Oncotype DX single gene scores for estrogen receptor (ER), progesterone receptor (PgR), and HER2 in HR+/HER2- breast cancer. METHODS: We retrospectively analyzed 260 patients with HR+/HER2- breast cancer who underwent surgery and Oncotype DX testing at Saitama Medical University International Medical Center between January 2022 and October 2024. TILs were evaluated on hematoxylin and eosin-stained slides according to the International TILs Working Group 2014 guidelines, with high TILs defined as 10%. Associations between TILs, clinicopathological factors, and Oncotype DX single gene scores were examined using statistical analyses, including logistic regression. Additionally, publicly available data from The Cancer Genome Atlas (TCGA) cohort were analyzed for validation. RESULTS: High TIL levels were observed in 32 cases (12.3%). Tumors with high TILs showed significantly lower Oncotype DX single gene expression of ER (9.8 1.9 vs. 10.5 1.3, p < 0.01), PgR (6.3 2.2 vs. 7.4 1.8, p < 0.01), and HER2 (8.5 0.7 vs. 9.2 0.6, p < 0.001) compared with tumors with low TILs. Multivariate analysis identified node-negative status (odds ratio [OR]: 0.266; p = 0.0159) and lower HER2 single gene expression (OR: 0.293; p = 0.00144) as independent predictors of high TILs. TCGA analysis confirmed that lower HER2 mRNA expression was associated with increased chemokine gene expression. DISCUSSION: In HR+/HER2- breast cancer, tumors with lower HER2 mRNA expression exhibit higher lymphocytic infiltration, suggesting the presence of a distinct immunologically active subset. Oncotype DX single gene scores, particularly HER2, may provide information beyond recurrence risk prediction and help identify patients who may benefit from immune-modulating therapeutic strategies.

论文信息

作者: Ohara M、Mikami E、Inohana W、Kurosawa T、Nakame A、Sakakibara A、Ichinose Y、Fujimoto A
单位: Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.Japan
期刊: Frontiers in oncology2026

原文标识: PubMed 41675290　·　DOI 10.3389/fonc.2026.1677929

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