P1-5-61 - Characterization of serum HER2 extracellular domain (ECD) level in patients with metastatic colorectal cancer

Abstract

Background: Overexpression of human epidermal growth factor receptor (HER) 2 occurs in approximately 20% of breast or gastric, and 5% of colorectal cancers. Moreover,activation of the HER2 pathway has been reported to be one of the mechanisms of primary or acquired resistace to anti-EGFR antibodies in RAS wild-type metastatic colorectal cancer (mCRC). The serum level of the HER2 extracellular domain (ECD) is used as a tumor marker or surrogate marker of the HER2 status in gastric and breast cancers. However, little is known about HER2-ECD levels and its characterization in mCRC patients (pts).Methods: We prospectively analyzed consecutive mCRC pts receiving palliative chemotherapy in our hospital. HER2-ECD level was measured in blood serum, and its positivity was defined as a serum HER2 level> 15.2 ng/ml, based on the manufacturers' recommended cutoff value.Results: A total of 145 pts were enrolled in this study. Pt characteristics were as follows: males/females (55%/45%), median age (range); 64 (24- 93) years, primary site; colon/rectum (52%/48%), RAS status; wild/RAS mutant/BRAF mutant/ unknown (57%/31%/5%/8%). The positive rate of HER2 ECD, CEA, and CA19-9 were 27.6, 80.0 and 51.7%, respectively. HER2 ECD showed a linear relationship with CEA level (correlation coefficient of 0.677). Regarding the association with the RAS status, serum levels of HER2 ECD in RAS wild type pts were higher than those in RAS mutant pts (positive rate of 33 vs. 20%, respectively). Moreover, in RAS wild type pts, pts resistant to anti-EGFR antibody within 1 year showed a higher positive rate of HER2 ECD than the others (55 vs. 28%,respectively; p = 0.0311).Conclusions: A Non negligible number of mCRC pts were positive for serum levels of HER2 ECD. HER2 ECD may be associated with tumor burden and acquired resistance to anti-EGFR therapy, but further studies are necessary to determine clinical utility of HER2 ECD. Background: Overexpression of human epidermal growth factor receptor (HER) 2 occurs in approximately 20% of breast or gastric, and 5% of colorectal cancers. Moreover,activation of the HER2 pathway has been reported to be one of the mechanisms of primary or acquired resistace to anti-EGFR antibodies in RAS wild-type metastatic colorectal cancer (mCRC). The serum level of the HER2 extracellular domain (ECD) is used as a tumor marker or surrogate marker of the HER2 status in gastric and breast cancers. However, little is known about HER2-ECD levels and its characterization in mCRC patients (pts). Methods: We prospectively analyzed consecutive mCRC pts receiving palliative chemotherapy in our hospital. HER2-ECD level was measured in blood serum, and its positivity was defined as a serum HER2 level> 15.2 ng/ml, based on the manufacturers' recommended cutoff value. Results: A total of 145 pts were enrolled in this study. Pt characteristics were as follows: males/females (55%/45%), median age (range); 64 (24- 93) years, primary site; colon/rectum (52%/48%), RAS status; wild/RAS mutant/BRAF mutant/ unknown (57%/31%/5%/8%). The positive rate of HER2 ECD, CEA, and CA19-9 were 27.6, 80.0 and 51.7%, respectively. HER2 ECD showed a linear relationship with CEA level (correlation coefficient of 0.677). Regarding the association with the RAS status, serum levels of HER2 ECD in RAS wild type pts were higher than those in RAS mutant pts (positive rate of 33 vs. 20%, respectively). Moreover, in RAS wild type pts, pts resistant to anti-EGFR antibody within 1 year showed a higher positive rate of HER2 ECD than the others (55 vs. 28%,respectively; p = 0.0311). Conclusions: A Non negligible number of mCRC pts were positive for serum levels of HER2 ECD. HER2 ECD may be associated with tumor burden and acquired resistance to anti-EGFR therapy, but further studies are necessary to determine clinical utility of HER2 ECD.