HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.
| Title | HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Martin, V., Landi L., Molinari F., Fountzilas G., Geva R., Riva A., Saletti P., De Dosso S., Spitale A., Tejpar S., Kalogeras K. T., Mazzucchelli L., Frattini M., & Cappuzzo F. |
| Journal | Br J Cancer |
| Volume | 108 |
| Issue | 3 |
| Pagination | 668-75 |
| Date Published | 2013 Feb 19 |
| ISSN | 1532-1827 |
| Keywords | Adenocarcinoma, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms, Female, Follow-Up Studies, Gene Amplification, Gene Dosage, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Mutation, Prognosis, Proto-Oncogene Proteins, ras Proteins, Receptor, ErbB-2, Retrospective Studies, Survival Rate |
| Abstract | BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease.METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab.RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively).CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients. |
| DOI | 10.1038/bjc.2013.4 |
| Alternate Journal | Br. J. Cancer |
| PubMed ID | 23348520 |
| PubMed Central ID | PMC3593567 |
