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HER2阳性乳腺癌脑转移预后风险分层模型的建立及其在指导治疗决策中的意义。

Development of a prognostic risk stratification model for HER2-positive breast cancer brain metastasis and its implications in guiding treatment decisions.

作者信息

Chen Jiaxin, Sh Yuan, Dong Danfeng, Yan Huicui, Zhang Huiqiang, Wu Zisheng, Zhou Jinmei, Wu Xuexue, Chu Fei, Jiang Zefei, Li Shanhu, Yang Jin, Xu Ling, Wang Tao

机构信息

Breast Cancer Department, The Fifth Medical Center of PLA General Hospital, Beijing, China.

Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing, China.

出版信息

Sci Rep. 2025 Jul 2;15(1):22623. doi: 10.1038/s41598-025-06645-y.


DOI:10.1038/s41598-025-06645-y
PMID:40596412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12215926/
Abstract

Brain metastasis occurs in approximately 50% of patients with advanced HER2-positive breast cancer. Despite improved prognosis, survival remains limited. This study aims to investigate the clinicopathological characteristics of HER2-positive breast cancer brain metastasis (BCBM) patients and their prognostic associations, to identify personalized treatment strategies to enhance survival. This retrospective study included HER2-positive BCBM patients treated at three institutions: the Fifth Medical Center of the Chinese PLA General Hospital, Peking University First Hospital, and the First Affiliated Hospital of Xi'an Jiaotong University. Clinical, pathological, and treatment data were collected. A prognostic model was developed using recursive variable selection, starting with significant variables from univariate analysis and refining them through a recursive loop in multivariate Cox regression. The model stratified patients into three risk groups: low-risk (score 0-1), intermediate-risk (score 2-3), and high-risk (score 4-6), based on various independent prognostic factors. The median survival times for the low-, intermediate-, and high-risk groups were 30, 20, and 10 months, respectively (P < 0.0001, HR = 1.35, 95% CI: 0.94-1.94; HR = 4.02, 95% CI: 2.4-6.73). The mean ROC curve AUC values for the 1-year, 2-year, and 3-year prognostic predictions were 0.69, 0.70, and 0.61, respectively. In the independent validation cohort of 75 patients, prognostic stratification into low-, intermediate-, and high-risk groups revealed significant differences in outcomes (73 months vs. 35 months vs. 9 months, P < 0.001, HR = 2.68, 95% CI: 1.30-5.52; HR = 8.82, 95% CI: 3.89-19.97). The mean AUC value for the 1-year and 2-year prognostic predictions in the validation cohort was 0.94, whereas the mean AUC value for the 3-year prognostic prediction was 0.81. This study developed a prognostic stratification model for HER2-positive BCBM patients based on clinicopathological characteristics.

摘要

脑转移发生在约50%的晚期HER2阳性乳腺癌患者中。尽管预后有所改善,但生存期仍然有限。本研究旨在调查HER2阳性乳腺癌脑转移(BCBM)患者的临床病理特征及其预后相关性,以确定个性化治疗策略来提高生存率。这项回顾性研究纳入了在中国人民解放军总医院第五医学中心、北京大学第一医院和西安交通大学第一附属医院接受治疗的HER2阳性BCBM患者。收集了临床、病理和治疗数据。使用递归变量选择方法建立了一个预后模型,从单因素分析中的显著变量开始,并通过多变量Cox回归中的递归循环对其进行优化。该模型根据各种独立的预后因素将患者分为三个风险组:低风险(评分0 - 1)、中风险(评分2 - 3)和高风险(评分4 - 6)。低、中、高风险组的中位生存时间分别为30、20和10个月(P < 0.0001,HR = 1.35,95% CI:0.94 - 1.94;HR = 4.02,95% CI:2.4 - 6.73)。1年、2年和3年预后预测的平均ROC曲线AUC值分别为0.69、0.70和0.61。在75例患者的独立验证队列中,分为低、中、高风险组的预后分层显示出结局的显著差异(73个月对35个月对9个月,P < 0.001,HR = 2.68,95% CI:1.30 - 5.52;HR = 8.82,95% CI:3.89 - 19.97)。验证队列中1年和2年预后预测的平均AUC值为0.94,而3年预后预测的平均AUC值为0.81。本研究基于临床病理特征为HER2阳性BCBM患者建立了一个预后分层模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/d64d3719ad03/41598_2025_6645_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/d5b503e96343/41598_2025_6645_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/3af03125e46c/41598_2025_6645_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/d64d3719ad03/41598_2025_6645_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/d5b503e96343/41598_2025_6645_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/3af03125e46c/41598_2025_6645_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd51/12215926/d64d3719ad03/41598_2025_6645_Fig3_HTML.jpg

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本文引用的文献

[1]
CSCO expert consensus on the diagnosis and treatment of breast cancer brain metastasis.

Transl Breast Cancer Res. 2022-7-30

[2]
Efficacy and safety of pyrotinib and radiotherapy . pyrotinib-based therapy in patients with HER2 breast cancer with brain metastasis: a retrospective cohort study.

Ann Transl Med. 2022-11

[3]
Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial.

Lancet. 2023-1-14

[4]
Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial.

JAMA Oncol. 2023-2-1

[5]
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis.

Cancer Discov. 2022-12-2

[6]
Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry.

ESMO Open. 2022-6

[7]
Management of Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO Guideline Update.

J Clin Oncol. 2022-8-10

[8]
Cancer statistics in China and United States, 2022: profiles, trends, and determinants.

Chin Med J (Engl). 2022-2-9

[9]
Targeting HER2+ Breast Cancer Brain Metastases: A Review of Brain-Directed HER2-Directed Therapies.

CNS Drugs. 2022-2

[10]
Targeting brain metastases in breast cancer.

Cancer Treat Rev. 2022-2

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