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一项评估血清HER2细胞外结构域在HER2过表达乳腺癌中的临床应用价值的前瞻性研究。

A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression.

作者信息

Reix Nathalie, Malina Charlotte, Chenard Marie-Pierre, Bellocq Jean-Pierre, Delpous Stéphanie, Molière Sébastien, Sevrin Anthony, Neuberger Karl, Tomasetto Catherine, Mathelin Carole

机构信息

ICube UMR 7357, Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.

Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France.

出版信息

Breast Cancer Res Treat. 2016 Nov;160(2):249-259. doi: 10.1007/s10549-016-4000-z. Epub 2016 Oct 5.

DOI:10.1007/s10549-016-4000-z
PMID:27709352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5065601/
Abstract

PURPOSE

We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression.

METHODS

We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up.

RESULTS

Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6-113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2-5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort.

CONCLUSIONS

HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cancer.

摘要

目的

我们探讨了人表皮生长因子受体2细胞外结构域（HER2/ECD）在接受HER2过表达浸润性乳腺癌治疗的患者中的临床应用价值。

方法

我们前瞻性研究了2007年至2014年间纳入的334名均接受曲妥珠单抗治疗的女性血清中的HER2/ECD水平。在诊断时、治疗期间以及随访过程中测量HER2/ECD水平。我们研究了诊断时HER2/ECD与其他临床病理参数的关系、其预后价值以及在新辅助治疗监测和随访期间的应用价值。

结果

诊断时HER2/ECD升高与肿瘤侵袭性相关参数呈正相关。诊断时HER2/ECD水平高的非转移性患者无病生存期显著缩短（HR = 13.6，95% CI 1.6 - 113.6，P < 0.0001）。HER2/ECD水平低的转移性患者无进展生存期更好（HR = 2.6，95% CI 1.2 - 5.3，P = 0.033）。多因素分析显示，诊断时HER2/ECD水平是一个独立的预后因素。在新辅助治疗期间，仅在组织学完全缓解组中报告HER2/ECD有显著下降（P = 0.031）。在随访期间，HER2/ECD有助于在18.6% 的研究队列病例中在影像学检查前预测复发、疾病进展和转移。

结论

HER2/ECD是一个预后因素，在评估新辅助治疗疗效方面具有重要价值。HER2/ECD似乎也是一种有助于早期诊断复发和预测转移转归的监测生物标志物。本研究为支持在HER2阳性乳腺癌管理中使用HER2/ECD提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/8c2d30eeb5be/10549_2016_4000_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/60f65c72eebf/10549_2016_4000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/8e44f03e8e6d/10549_2016_4000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/fc07767a078b/10549_2016_4000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/8c2d30eeb5be/10549_2016_4000_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/60f65c72eebf/10549_2016_4000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/8e44f03e8e6d/10549_2016_4000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/fc07767a078b/10549_2016_4000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25bb/5065601/8c2d30eeb5be/10549_2016_4000_Fig4_HTML.jpg

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