Invasive Lobular Carcinoma Has Higher Immune Response Than Invasive Ductal Carcinoma in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers.

IF 2.2 Q3 ONCOLOGY

World Journal of Oncology Pub Date : 2025-09-13 eCollection Date: 2025-10-01 DOI:10.14740/wjon2529

Gabrielle Yee, Rongrong Wu, Takashi Ishikawa, Kazuaki Takabe

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引用次数: 0

Abstract

Background: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are two major pathological diagnoses of breast cancer, but few studies have described their differences within luminal (estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative) subtypes at the molecular level.

Methods: Using The Cancer Genome Atlas (TCGA) (n = 584) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,355) cohorts, we analyzed luminal ILC and IDC, excluding mixed type, in patients with stage I-III breast cancer.

Results: ILC was associated with Nottingham histological grade 2, larger tumor size and more stage III disease than IDC (all P < 0.01) but no difference in lymph node nor distant metastasis in both cohorts. There was no survival difference between ILC and IDC. ILC had less aggressive genomic features compared to IDC, and the cell proliferation score and Ki67 gene expression were significantly lower in ILC in TCGA (P < 0.001); however, these findings were not validated in METABRIC. Hallmark cell proliferation-related gene sets (E2F targets, G2M checkpoint, MYC targets V1, and MTORC1 signaling) were significantly less enriched in ILC in both cohorts (all normalized enrichment score (NES) > 1.4, false discovery rate (FDR) < 0.12). While ILC appeared to have a lower trend of pathological complete response (pCR) in the GSE20194 and GSE1140494 cohorts, ILC was infiltrated with significantly more CD4⁺ cells and dendritic cells and significantly less T helper type I (Th1) cells, regulatory T cells and M1 and M2 macrophages in both cohorts (all P < 0.05). Stromal cells, adipocytes and lymphatic endothelial cells were highly infiltrated in ILC, and cytolytic activity that represented the global anti-tumor immunity was significantly elevated in ILC in TCGA and subsequently validated in METABRIC.

Conclusions: ILC has higher immune response and immune cell infiltration than IDC in the luminal subtype.

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在雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌中，浸润性小叶癌的免疫应答高于浸润性导管癌。

背景：浸润性小叶癌（Invasive lobular carcinoma， ILC）和浸润性导管癌（Invasive ductal carcinoma， IDC）是乳腺癌的两种主要病理诊断，但很少有研究在分子水平上描述它们在腔内（雌激素受体（ER）阳性/人表皮生长因子受体2 （HER2）阴性）亚型之间的差异。方法：使用癌症基因组图谱（TCGA）（n = 584）和乳腺癌国际联盟分子分类学（METABRIC）（n = 1355）队列，我们分析了I-III期乳腺癌患者的腔内ILC和IDC，不包括混合型。结果：与IDC相比，ILC与Nottingham组织学2级、肿瘤大小更大、III期疾病更多相关（均P < 0.01），但两组患者的淋巴结和远处转移无差异。ILC和IDC之间没有生存差异。与IDC相比，ILC具有较低的侵袭性基因组特征，TCGA中ILC的细胞增殖评分和Ki67基因表达显著降低（P < 0.001）；然而，这些发现并未在METABRIC中得到验证。在两个队列中，标志性细胞增殖相关基因集（E2F靶点、G2M检查点、MYC靶点V1和MTORC1信号）在ILC中的富集程度显著降低（所有归一化富集评分（NES） bb0 1.4，错误发现率(FDR) < 0.12）。虽然在gse201194和GSE1140494队列中，ILC的病理完全反应（pCR）趋势较低，但在两个队列中，ILC中CD4+细胞和树突状细胞的浸润量均显著增加，T辅助I型（Th1）细胞、调节性T细胞和M1、M2巨噬细胞的浸润量均显著减少（P < 0.05）。ILC中基质细胞、脂肪细胞和淋巴内皮细胞高度浸润，TCGA中ILC中代表整体抗肿瘤免疫的细胞溶解活性显著升高，随后在METABRIC中得到验证。结论：在腔室亚型中，ILC的免疫应答和免疫细胞浸润高于IDC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.