Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer
Open accessAbstract
BACKGROUND: To investigate whether copy number gain of MET or hepatocyte growth factor (HGF) affect trastuzumab sensitivity in HER2-positive metastatic breast cancer (MBC). METHODS: We analysed 130 HER2-positive MBC treated with trastuzumab-based therapy. MET and HGF gene copy numbers (GCN) were assessed by fluorescence in situ hybridisation (FISH) in primary breast cancer samples. Receiver operating characteristic analysis was applied to find the best cutoff point for both MET and HGF GCN. RESULTS: MET FISH-positive cases (N=36, mean 3.72) had a significantly higher trastuzumab failure rate (44.4% vs 16.0%; P=0.001) and a significantly shorter time to progression (5.7 vs 9.9 months; HR 1.74; P=0.006) than MET FISH-negative cases (N=94, mean <3.72). Hepatocyte growth factor GCN was evaluated in 84 cases (64.6%). Receiver operating characteristic analysis identified 33 HGF FISH-positive patients (mean HGF GCN 3.01). HGF FISH-positive status was significantly associated with higher risk of failure (30.3% vs 7.8%; P=0.007) as compared with HGF FISH-negative cases (N=51, mean <3.01). MET and HGF FISH-positive status was highly correlated (P<0.001) and combination of both biomarkers did not increase predictive value of either considered separately. CONCLUSION: High GCNs of MET and HGF associate with an increased risk of trastuzumab-based therapy failure in HER2-positive MBC.
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Gene amplification of MET and HGF was reported in a cohort of HER2+ patients who did not respond to trastuzumab and chemotherapy.
“Further, gene amplification of MET and HGF was reported in a cohort of HER2+ patients who did not respond to trastuzumab and chemotherapy (Minuti et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Minuti et al., 2012
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References 44 · Cited by 127
Research works printed but not linked: 3
- Cappuzzo F, Marchetti A, Skokan M, Rossi E, Gajapathy S, Felicioni L, Del Grammastro M, Sciarrotta MG, Buttitta F, Incarbone M, Toschi L, Finocchiaro G, Destro A, Terracciano L, Roncalli M, Alloisio M, Santoro A, Varella-Garcia M (2009) Incresed MET gene copy number negativly affects survival of surgical resected non-small cell lung cancer. J Clin Oncol 27: 1667–1674 19255323 PMC3341799
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- Authors
- Minuti, G., Cappuzzo, F., Duchnowska, R., Jassem, J., Fabi, A., O’Brien, T., Mendoza, A. D., Landi, L., Biernat, W., Czartoryska-Arłukowicz, B., Jankowski, T., Zuziak, D., Zok, J., Szostakiewicz, B., Foszczyńska-Kłoda, M., Tempińska-Szałach, A., Rossi, E., & Varella-Garcia, M.
- Affiliations
- Ospedale di Livorno (IT)
- Wojskowy Instytut Medyczny (PL)
- Gdańsk Medical University (PL)
- Instituto Nazionale Tumori Regina Elena (IT)
- University of Colorado Cancer Center (US)
- Lublin Oncology Center (PL)
- Beskidzkie Centrum Onkologii Szpital Miejski im. Jana Pawla II w Bielsku-Bialej (PL)
- Corresponding author
- Cappuzzo, F
- ORCID
- Venue
- British Journal of Cancer
- Published
- 2012-07-31
- Volume
- 107
- Issue
- 5
- Pages
- 793-799
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3425981
- OpenAlex
- W2101574075
- Cited by
- 127
- References
- 44
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 16 · 2019: 4 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 15 · 2014: 15 · 2013: 8 · 2012: 2
- FWCI
- 6.33
- 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)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- National Cancer Institute (P30 CA46934, CA-46934, P30CA046934)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- hepatocyte growth factor, trastuzumab resistance, HER2-positive breast cancer, metastatic breast cancer, predictive biomarkers, time to progression
- MeSH terms
- Trastuzumab, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Immunohistochemistry, Middle Aged, Prognosis, Retrospective Studies, Hepatocyte Growth Factor, In Situ Hybridization, Fluorescence, Gene Dosage, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Antibodies, Monoclonal, Humanized
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