Effects of breast cancer risk factors on the tumor microenvironment: a morphological deep-learning analysis of three prospective cohorts.

IF 8.4 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2026-06-22 DOI:10.1038/s41523-026-00994-1

Clara Bodelon, Mohamed Amgad, James M Hodge, Maha A T Elsebaie, Mariah Landry, Cheng Peng, Rulla M Tamimi, Peter Kraft, Lauren E McCullough, Mark E Sherman, Mia M Gaudet, Alpa V Patel, Lee A D Cooper, Lauren R Teras

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Abstract

Emerging evidence suggests a critical role of the tumor microenvironment (TME) in breast cancer (BC) development and outcomes, yet factors that modify the TME are poorly understood. We investigated the relationship between BC etiological factors and the tumor and TME using 110 histological features of the epithelium, stroma, and immune infiltration, computationally quantified in 3724 H&E slides from three prospective cohort studies. Age, race, hormonal, and lifestyle factors were associated with features of the breast TME. Menopausal hormone therapy was associated with epithelial and stromal features found in less aggressive tumors, while higher body mass index (BMI) was associated with two histological features not captured by grade, and both were associated with poor prognosis. These two features mediated the BMI and BC-specific mortality association by 18.1%. Our findings provide novel insights into the role of etiological factors on the TME including modifiable factors that have implications for prevention and outcomes.

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乳腺癌危险因素对肿瘤微环境的影响：三个前瞻性队列的形态学深度学习分析。

新出现的证据表明，肿瘤微环境（TME）在乳腺癌（BC）的发展和结局中起着关键作用，但对改变TME的因素知之甚少。我们利用来自三个前瞻性队列研究的3724张H&E切片计算量化的上皮、间质和免疫浸润的110个组织学特征，研究了BC病因与肿瘤和TME之间的关系。年龄、种族、激素和生活方式因素与乳房TME的特征有关。绝经期激素治疗与侵袭性较低肿瘤的上皮和间质特征相关，而较高的体重指数（BMI）与两种未被分级捕获的组织学特征相关，两者都与预后不良相关。这两个特征介导了BMI和bc特异性死亡率之间18.1%的关联。我们的研究结果为病因因素在TME中的作用提供了新的见解，包括对预防和结果有影响的可改变因素。

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

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.