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探索HER2阳性转移性乳腺癌的预后因素:一项在瑞士一家大型医院进行的回顾性队列研究。

Exploring prognostic factors for HER2-positive metastatic breast cancer: a retrospective cohort study in a major Swiss hospital.

作者信息

Bringolf Lilian, Pestalozzi Bernhard, Fink Daniel, Dedes Konstantin

机构信息

Department of Gynaecology, University Hospital of Zurich, Switzerland.

Department of Medical Oncology, University Hospital of Zurich, Switzerland.

出版信息

Swiss Med Wkly. 2016 Dec 19;146:w14393. doi: 10.4414/smw.2016.14393. eCollection 2016.

Abstract

BACKGROUND

Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment.

PATIENTS AND METHODS

This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81). Overall survival (OS) and other time-to-event endpoints were determined with Kaplan-Meier curves and clinicopathological factors predicting long-term outcome were identified by use of the log-rank test.

RESULTS

The median OS for the cohort was 5.9 years (95% confidence interval [CI] 3.5-8.3). Twenty patients (28.6%) remained in complete remission after 1 year, 11 (15.7%) after 2 years and 4 (5.7%) beyond 5 years. The median progression-free survival was 13.6 months (95% CI 9.0-18.3). The objective response rate (ORR) was 60.5% with 16 (19.8%) complete responses and 33 (40.8%) partial responses. Six (7.4%) patients had brain metastases as first site of relapse and they had a median OS of 1.9 years (95% CI 1.7-2.2 years). Thirty-four of all 81 patients (42%) had developed brain metastases by the time of death or last follow-up. Median OS after diagnosis of brain metastases was 26 months (95% CI 19.9-32.0). Only primary brain metastases were found to be a prognostic marker associated with shorter overall survival. Hormone-receptor status and presence of visceral metastases at primary diagnosis were not associated with prognosis. Only four patients (4.9%) developed some degree of left ventricular dysfunction under treatment with trastuzumab.

CONCLUSIONS

HER2-targeted treatment has improved the overall survival of patients with HER2-postive metastatic breast cancer with median OS exceeding 5 years. There are, however, no predictive markers for a long-term survival. Only the absence of primary brain metastases seems to be an indicator of a good prognosis.

摘要

背景

曲妥珠单抗(赫赛汀®,罗氏公司)显著改善了HER2阳性转移性乳腺癌患者的预后。一些患者可保持多年缓解状态。然而,目前尚无与长期生存相关的预后标志物。本研究旨在分析单中心HER2阳性转移性乳腺癌的治疗模式,并探索HER2靶向治疗后长期生存的预后因素。

患者与方法

这是一项回顾性队列研究,纳入了2004年至2014年间在苏黎世大学医院接受一线HER2靶向治疗的所有HER2阳性转移性乳腺癌患者(n = 81)。采用Kaplan-Meier曲线确定总生存期(OS)和其他事件发生时间终点,并通过对数秩检验确定预测长期预后的临床病理因素。

结果

该队列的中位OS为5.9年(95%置信区间[CI] 3.5 - 8.3)。20例患者(28.6%)在1年后仍处于完全缓解状态,11例(15.7%)在2年后仍处于完全缓解状态,4例(5.7%)在5年后仍处于完全缓解状态。中位无进展生存期为13.6个月(95% CI 9.0 - 18.3)。客观缓解率(ORR)为60.5%,其中16例(19.8%)为完全缓解,33例(40.8%)为部分缓解。6例(7.4%)患者以脑转移作为首发复发部位,其OS中位数为1.9年(95% CI 1.7 - 2.2年)。在81例患者中,有34例(42%)在死亡或最后一次随访时已发生脑转移。脑转移诊断后的中位OS为26个月(95% CI 19.9 - 32.0)。仅发现原发性脑转移是与总生存期较短相关的预后标志物。激素受体状态和初诊时内脏转移的存在与预后无关。在曲妥珠单抗治疗期间,只有4例患者(4.9%)出现了一定程度的左心室功能障碍。

结论

HER2靶向治疗改善了HER2阳性转移性乳腺癌患者的总生存期,中位OS超过5年。然而,尚无长期生存的预测标志物。仅无原发性脑转移似乎是预后良好的一个指标。

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