title: Met and its ligand HGF are associated with clinical outcome in breast cancer.
abstract: Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo- or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre- and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the pre-menopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested.
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Veenstra
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Gizeh
authors.initials: G
authors.lastname: Pérez-Tenorio
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Stelling
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Karlsson
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Sanam Mirwani
authors.initials: SM
authors.lastname: Mirwani
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nordensköljd
authors.affiliation: Department of Oncology-Pathology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Fornander
authors.affiliation: Department of Clinical and Experimental Medicine and Department of Oncology, Linköping University, Linköping, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010766:Phosphorylation; D017698:Postmenopause / Q000235:genetics; D017697:Premenopause / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: copy number variation; droplet digital PCR; radiation; radiotherapy; triple-negative breast cancer