HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
Open accessAbstract
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.
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Patients with tumors featuring HER2 amplification or heregulin overexpression and treated with cetuximab or panitumumab experienced disease progression and shorter progression-free and overall survival compared with HER2 wild-type cases.
“In retrospective studies, patients with tumors featuring HER2 amplification or heregulin overexpression and treated with cetuximab or panitumumab experienced disease progression and shorter progression-free and overall survival compared with HER2 wild-type cases [91-93].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [93]
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Self-citation
- 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.
- Affiliations
- Istituto Cantonale di Patologia (CH)
- Ospedale di Livorno (IT)
- Aristotle University of Thessaloniki (GR)
- Tel Aviv Sourasky Medical Center (IL)
- Istituto Oncologico della Svizzera Italiana (CH)
- Universitair Ziekenhuis Leuven (BE)
- Corresponding author
- Frattini, M
- Venue
- British Journal of Cancer
- Published
- 2013-01-24
- Volume
- 108
- Issue
- 3
- Pages
- 668-675
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3593567
- OpenAlex
- W2034338421
- Cited by
- 156
- References
- 34
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 9 · 2020: 15 · 2019: 15 · 2018: 17 · 2017: 17 · 2016: 11 · 2015: 9 · 2014: 12 · 2013: 4
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Oncosuisse
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- HER2 gene copy number, metastatic colorectal cancer, anti-EGFR monoclonal antibody, cetuximab, panitumumab, KRAS wild-type, predictive biomarkers, HER2 amplification, polysomy, progression-free survival, overall survival
- MeSH terms
- Cetuximab, Panitumumab, Adenocarcinoma, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Female, Follow-Up Studies, Gene Amplification, Humans, Male, Middle Aged, Mutation, Prognosis, Proto-Oncogene Proteins, Retrospective Studies, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Survival Rate, Proto-Oncogene Proteins p21(ras), In Situ Hybridization, Fluorescence, Gene Dosage, ras Proteins, Erb-b2 Receptor Tyrosine Kinases, Antibodies, Monoclonal, Humanized
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