蒽环类药物对早期乳腺癌的长期影响，微小RNA分析用于早期心脏毒性的关联研究。

Long-term impact of anthracycline in early-stage breast cancer, bridging of MiRNAs profiler for early cardiotoxicity.

作者信息

Poovorawan Nattaya, Susiriwatananont Thiti, Teerapakpinyo Chinachote, Chariyavilaskul Pajaree, Sitthideatphaiboon Piyada, Jarutasnangkul Luxica, Tumkosit Monravee, Chattranukulchai Pairoj, Theerasuwipakorn Nonthikorn, Aporntewan Chatchawit, Shuangshoti Shanop, Manasnayakorn Sopark, Vinayanuwattikun Chanida, Vorasettakarnkij Yongkasem, Sriuranpong Virote

机构信息

Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Chula GenePRO Center, Research Affairs, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

出版信息

Cardiooncology. 2025 Apr 23;11(1):39. doi: 10.1186/s40959-025-00337-2.

DOI:10.1186/s40959-025-00337-2

PMID:40270054

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12016148/

Abstract

BACKGROUND

Anthracyclines are essential in early breast cancer chemotherapy but pose long-term cardiotoxicity risks.

OBJECTIVES

This study aims to investigate the long-term incidence of cancer therapy-related cardiac dysfunction (CTRCD), bridging with the miRNAs profiler representing acute cardiac injury.

METHODS

We conducted a prospective cohort including stage I-III breast cancer patients who received anthracycline between 2007 and 2012. Echocardiography was performed before and 12 weeks after anthracycline administration. The miRNAs profiler was conducted by NanoString and RT-PCR. Long-term cardiac magnetic resonance imaging (CMR) was evaluated in 24.2% of asymptomatic participants.

RESULTS

At a median follow-up of 11 [IQR 6-12] years, 194 patients who completed follow-up echocardiography after anthracycline were included in the analysis. The median age at diagnosis was 50 [26-72] years. An early LVEF decline of ≥ 10% was found in 32.9% of participants. The cumulative equivalent dose of doxorubicin was 223.2 ± 21.6 mg/m2. At the time of censoring, sixty-four participants (32.9%) died, 70% from breast cancer. Nine participants (4.6%) reported cardiovascular events compatible with the CTRCD definition. Forty-seven participants (24.2%) underwent long-term cardiac evaluation. The miRNAs profiler and RT-PCR at different time points, 3 weeks and 6 weeks, respectively, revealed significantly diverse expressions of miR-1-3p and miR-16-5p in participants with and without an early LVEF decline of ≥ 10%. Despite cardiac injury demonstrated by dynamic miR-1-3p and miR-16-5p, CMR parameters revealed no significant differences.

CONCLUSIONS

Our study demonstrates a very low incidence of long-term symptomatic CTRCD. The diverse expression patterns of miR-16-5p and miR-1-3p at different time points also provide valuable biological insights. Within-normal results of an exact and comprehensive CMR, in asymptomatic and any LVEF change participants, indicate the long-term safety of limited-dose anthracycline-containing use.

摘要

背景

蒽环类药物在早期乳腺癌化疗中至关重要，但存在长期心脏毒性风险。

目的

本研究旨在调查癌症治疗相关心脏功能障碍（CTRCD）的长期发生率，并结合代表急性心脏损伤的微小RNA（miRNA）分析。

方法

我们进行了一项前瞻性队列研究，纳入2007年至2012年间接受蒽环类药物治疗的I-III期乳腺癌患者。在给予蒽环类药物前及给药后12周进行超声心动图检查。通过NanoString和逆转录聚合酶链反应（RT-PCR）进行miRNA分析。对24.2%无症状参与者进行了长期心脏磁共振成像（CMR）评估。

结果

在中位随访11[四分位间距6-12]年时，194例蒽环类药物治疗后完成随访超声心动图检查的患者纳入分析。诊断时的中位年龄为50[26-72]岁。32.9%的参与者出现早期左心室射血分数（LVEF）下降≥10%。多柔比星的累积等效剂量为223.2±21.6mg/m²。在审查时，64名参与者（32.9%）死亡，70%死于乳腺癌。9名参与者（4.6%）报告了符合CTRCD定义的心血管事件。47名参与者（24.2%）接受了长期心脏评估。分别在3周和6周不同时间点进行的miRNA分析和RT-PCR显示，早期LVEF下降≥10%和未下降的参与者中，miR-1-3p和miR-16-5p的表达存在显著差异。尽管动态miR-1-3p和miR-16-5p显示有心脏损伤，但CMR参数无显著差异。