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

Abstract For 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 ( ctc HER2+/‐) 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, ctc HER2+ has more favorable survivals than ctc HER2– (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 ctc HER2–) show a higher progression disease rate (60.0%, 0.0%; p = 0.0106). Therefore, CTC enumeration and ctc HER2 phenotyping may be prognostic and predictive biomarkers for HER2+ mCRC with anti‐HER2 therapy.