HER2 Expression in Circulating Tumor Cells as Prognostic and Predictive Biomarkers for Anti‐HER2 Therapy in Previously Treated Metastatic Colorectal Cancer

Author:

Wang Mengting12,Xu Ting3,Shen Lin3,Li Jian3,Zhu Ling12,Wang Chen12,Hu Zhiyuan12,Li Ping12,Yang Yanlian12ORCID,Wang Xicheng3

Affiliation:

1. CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology No. 11, Beiyitiao Beijing 100190 China

2. University of Chinese Academy of Sciences 19 A Yuquan Rd Beijing 100049 China

3. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing 100142 China

Abstract

AbstractFor human epidermal growth factor receptor 2‐positive metastatic colorectal cancer (HER2+ mCRC), anti‐HER2 therapy shows benefits, while current HER2 testing using tumor biopsy remains controversial. Noninvasive circulating tumor cells (CTCs) may achieve more accurate HER2 diagnosis . Herein, enumeration and HER2 phenotyping on CTCs (HER2(0/1+/2+/3+) CTCs) are assessed using TUMORFISHER for 40 mCRC patients (20 HER2+; 20 HER2‐negative). Positive/negative HER2 phenotypes on CTCs (ctcHER2+/‐) are determined with or without > 5% HER2(2+/3+) CTCs. After anti‐HER2 therapy, HER2+ patients without baseline CTCs show significantly better survivals than those with 1 ≤ CTCs ≤ 51 or ≥ 52 CTCs at baseline (mPFS; 5.6, 4.2, and 2.0 months; p = 0.0021) (mOS; not yet reached, 18.0 and 9.1 months; p = 0.0002). Among HER2+ patients with 1 ≤ CTCs ≤ 51 at baseline, ctcHER2+ has more favorable survivals than ctcHER2– (mPFS; 5.1 and 2.3 months; p = 0.0257) (mOS; not yet reached, 14.7 months; p = 0.0400). HER2+ patients with ≥ 52 CTCs or (with 1 ≤ CTCs ≤ 51 and maintained ctcHER2–) show a higher progression disease rate (60.0%, 0.0%; p = 0.0106). Therefore, CTC enumeration and ctcHER2 phenotyping may be prognostic and predictive biomarkers for HER2+ mCRC with anti‐HER2 therapy.

Publisher

Wiley

Subject

Pharmacology (medical),Biochemistry (medical),Genetics (clinical),Pharmaceutical Science,Pharmacology,Medicine (miscellaneous)

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