title: Quantitation of HER2 expression or HER2:HER2 dimers and differential survival in a cohort of metastatic breast cancer patients carefully selected for trastuzumab treatment primarily by FISH.
abstract: The selection of patients with HER2-positive breast cancer for treatment with trastuzumab is based on the measurement of HER2 protein expression by immunohistochemistry, or the presence of HER2 gene amplification by fluorescence in situ hybridization (FISH). By using multivariate analyses, we investigate the relationship between quantitative measurements of HER2 expression or HER2:HER2 dimers and objective response (Response Evaluation Criteria in Solid Tumors), time to progression, and breast cancer survival after trastuzumab treatment in a cohort of patients with metastatic breast cancer who were primarily selected for treatment by FISH. The VeraTag assay, a proximity-based assay designed to quantitate protein expression and dimerization in formalin-fixed, paraffin-embedded tissue specimens, was used to measure HER2 protein expression and HER2:HER2 dimer levels. In a Cox proportional hazards analysis, higher HER2 expression or HER2:HER2 dimer levels were both correlated with longer survival (P=0.0058 and P=0.016, respectively) after treatment with trastuzumab in a population of patients that were either FISH-positive (90%) or immunohistochemistry 3+ (10%). Patients with higher levels of HER2 expression or HER2:HER2 dimers seemed to derive little benefit from the addition of concomitant chemotherapy to trastuzumab, whereas those with lower levels benefited significantly [interaction test P=0.43 (HER2 expression), P=0.27 (HER2:HER2 dimers)]. These data suggest that more quantitative or functional measurements of HER2 status may facilitate the development of more personalized treatment strategies for patients with metastatic breast cancer.
authors.affiliation: Department of Medical Oncology, Jules Bordet Institute, Brussels.
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Jeff
authors.initials: J
authors.lastname: Sperinde
authors.forename: Fanny
authors.initials: F
authors.lastname: Piette
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.forename: Xueguang
authors.initials: X
authors.lastname: Jin
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tan
authors.forename: Virginie
authors.initials: V
authors.lastname: Durbecq
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Rosa
authors.initials: R
authors.lastname: Giuliani
authors.forename: Colombe
authors.initials: C
authors.lastname: Chappey
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: John
authors.initials: J
authors.lastname: Winslow
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Christos
authors.initials: C
authors.lastname: Petropoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Bates
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001940:Breast / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008875:Middle Aged; D055503:Protein Multimerization; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human