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

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 (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 & LE; CTCs & LE; 51 or & GE; 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 & LE; CTCs & LE; 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 & GE; 52 CTCs or (with 1 & LE; CTCs & LE; 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.