title: HER2 status in a population-derived breast cancer cohort: discordances during tumor progression.
abstract: This retrospective study investigates the correlation of intra-individual HER2 status between primary breast cancers and corresponding recurrences in a population derived cohort. The REMARK criteria were used as reference. In 151 breast cancer patients, primary tumors were analyzed for HER2 status on histopathology sections using immunohistochemistry (IHC) confirmed by fluorescence in situ hybridization (FISH) for IHC 2+ and 3+. Recurrences (loco regional and distant) were investigated by aspiration cytology, using HER2 immunocytochemistry (ICC) or FISH (ICC in 84 patients and FISH in 102 patients). In the 151 patients, sites of recurrence were bone/bone marrow 30%, liver 16%, local recurrence 18%, lung/pleura 10%, axillary lymph nodes 9%, skin (non-local) 7%, supra clavicular lymph nodes 5%, and other sites 7%. In 15 patients (10%) HER2 status changed, 7 of 108 patients (6%) from HER2 negative to HER2 positive and 8 of 43 (19%) from HER2 positive to HER2 negative. Intra-patient agreement in HER2 status was 76% (95% CI 64-87%), and the disagreement was 10% (95% CI 5-15%). The multivariable Cox analysis showed a significantly increased risk of dying in the patient group with changed HER2 status compared to patients with concordant positive HER2 status. Overall survival HR is 5.47 (95% CI 2.01-14.91) and survival from relapse HR is 3.22 (95% CI 1.18-8.77). The unstable status for HER2 in breast cancer is clinically significant and should motivate more frequent testing of recurrences.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet & Cancer Center Karolinska, Stockholm, Sweden. ulla.wilking@telia.com
authors.forename: Ulla
authors.initials: U
authors.lastname: Wilking
authors.forename: Eva
authors.initials: E
authors.lastname: Karlsson
authors.forename: Lambert
authors.initials: L
authors.lastname: Skoog
authors.forename: Thomas
authors.initials: T
authors.lastname: Hatschek
authors.forename: Elisabet
authors.initials: E
authors.lastname: Lidbrink
authors.forename: Goran
authors.initials: G
authors.lastname: Elmberger
authors.forename: Hemming
authors.initials: H
authors.lastname: Johansson
authors.forename: Linda
authors.initials: L
authors.lastname: Lindström
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009364:Neoplasm Recurrence, Local; D016609:Neoplasms, Second Primary / Q000737:chemistry* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human