Transcriptomic and microenvironment characteristics of triple-negative breast cancer under three different neoadjuvant treatment regimens.

IF 3 3区医学 Q2 ONCOLOGY

Breast Cancer Research and Treatment Pub Date : 2025-11-01 Epub Date: 2025-08-27 DOI:10.1007/s10549-025-07810-7

Zhilin Liu, Zhen Liu, Miaozhou Wang, Yaobang Liu, Xiaofeng Zhou, Yongxin Li, Zijun Zhu, Jinming Li, Jingqi Han, Yujin Hou, Bowen Zhao, Weiwei Zhang, Fuxing Zhao, Dengfeng Ren, Zitao Li, Yongzhi Chen, Shifen Huang, Mengting Da, Xiaoyan Ma, Xiaofang Ma, Ronghua Wang, Qiuxia Dong, Liang Cui, Jing Bai, Guoshuang Shen, Jiuda Zhao

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引用次数: 0

Abstract

Background: Adding immunotherapy to chemotherapy can modestly improve the pathological complete response (pCR) rate in triple-negative breast cancer (TNBC), while our previous NeoSAC study demonstrated that combining anti-angiogenic therapy can further enhance pCR. However, research on the mechanisms underlying the efficacy differences and biomarker comparisons across these treatment regimens remains insufficient.

Patients and methods: Female TNBC patients were consecutively enrolled into three groups: chemotherapy (chemo), chemo-immunotherapy (chemo-ICI), and chemo-immunotherapy-anti-angiogenesis (chemo-ICI-AA, from our NeoSAC study, NCT04722718). Efficacy and safety were compared, with RNA sequencing and immune microenvironment analyses conducted to explore mechanisms of efficacy differences and identify potential biomarkers.

Results: The total pCR rates in the chemo, chemo-ICI, and chemo-ICI-AA groups were 43.3%, 60.0%, and 72.7%, respectively. Baseline immune profiles were similar across groups, with comparable stromal, immune, and GEP scores. In the chemo-ICI-AA group, higher CD8 + T cells, TH1 cells, and TIL infiltration in pCR patients suggested their potential as biomarkers. Enhanced cytolytic activity, pro-inflammatory pathways, T-cell costimulation, and oxeiptosis correlated with higher pCR rates in the chemo-ICI-AA group. Notably, oxeiptosis has emerged as a potential predictor of treatment response, especially in pCR patients from the chemo-ICI and chemo-ICI-AA groups. Additionally, ALK (p = 0.017) and ATP6V1C2 (p = 0.036) were identified as significant genes in the chemo-ICI-AA pCR group, with predictive value for pCR outcomes.

Conclusion: Adding immunotherapy and anti-angiogenic therapy to chemotherapy progressively increased the pCR rate. We emphasized the critical role of differentially expressed genes and immune microenvironment changes in predicting treatment outcomes.

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三阴性乳腺癌在三种不同新辅助治疗方案下的转录组学和微环境特征

背景：化疗联合免疫治疗可适度提高三阴性乳腺癌（TNBC）的病理完全反应（pCR）率，而我们之前的NeoSAC研究表明，联合抗血管生成治疗可进一步提高pCR。然而，对这些治疗方案的疗效差异和生物标志物比较的潜在机制的研究仍然不足。患者和方法：女性TNBC患者被连续分为三组：化疗（chemo）、化疗免疫治疗（chemo- ici）和化疗免疫治疗-抗血管生成（chemo- ici - aa，来自我们的NeoSAC研究，NCT04722718）。通过RNA测序和免疫微环境分析来探讨疗效差异的机制和鉴定潜在的生物标志物。结果：化疗组、化疗- ici组和化疗- ici - aa组的总pCR率分别为43.3%、60.0%和72.7%。各组的基线免疫特征相似，基质、免疫和GEP评分相似。在chemo-ICI-AA组中，pCR患者中CD8 + T细胞、TH1细胞和TIL浸润较高，表明它们具有作为生物标志物的潜力。在化学- ici - aa组中，细胞溶解活性增强、促炎途径增强、t细胞共刺激和氧化凋亡与较高的pCR率相关。值得注意的是，上睑下垂已成为治疗反应的潜在预测因素，特别是在化疗- ici组和化疗- ici - aa组的pCR患者中。此外，ALK （p = 0.017）和ATP6V1C2 （p = 0.036）在chemo-ICI-AA pCR组中被鉴定为重要基因，对pCR结果具有预测价值。结论：化疗中加入免疫治疗和抗血管生成治疗可使pCR率逐渐升高。我们强调了差异表达基因和免疫微环境变化在预测治疗结果中的关键作用。

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

Breast Cancer Research and Treatment 医学-肿瘤学

CiteScore

6.80

自引率

2.60%

发文量

342

审稿时长

1 months

期刊介绍： Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.