title: Hormone receptor status does not affect the clinical benefit of trastuzumab therapy for patients with metastatic breast cancer.
abstract: BACKGROUND
  Hormone receptor (HR) and HER2 signaling pathways are involved in the regulation of breast cancer proliferation. The impact of HR status on the clinical outcome of patients with HER2-overexpressing disease treated with the monoclonal antibody trastuzumab is unknown.
  
  
  METHODS
  To evaluate this, we conducted a retrospective analysis of 805 patients with metastatic breast cancer enrolled in 3 clinical trials comparing trastuzumab in combination with chemotherapy versus chemotherapy alone or trastuzumab monotherapy as first-, second-, or third-line treatment. Patients whose tumor samples overexpressed HER2 by fluorescence in situ hybridization (FISH) were stratified based on HR status, and clinical outcomes were compared.
  
  
  RESULTS
  Tumor samples from 596 of 805 patients were HER2overexpressing by FISH; 45% of these were HR-positive and 43% were HR-negative (HR status was unknown in 12%). Overall response rate (ORR) and time to progression (TTP) were significantly higher in patients treated with chemotherapy plus trastuzumab than in those treated with chemotherapy alone, irrespective of HR status. Median survival was longer for patients with HR-positive tumors receiving combination therapy compared with those with HR-negative tumors. In the trastuzumab monotherapy trials, ORR and TTP were similar for patients with HR-positive and HR-negative tumors. Median survival was longer for patients with HR-positive tumors compared with those with HR-negative tumors.
  
  
  CONCLUSIONS
  Hormone receptor status did not affect the clinical benefit of trastuzumab given as a single agent or combined with chemotherapy. The addition of trastuzumab to chemotherapy provides an improved clinical benefit compared with chemotherapy alone, regardless of HR status.
authors.affiliation: Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.forename: Barry
authors.initials: B
authors.lastname: Lembersky
authors.forename: Kathy
authors.initials: K
authors.lastname: Schiffman
authors.forename: Grazyna
authors.initials: G
authors.lastname: Lieberman
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Paton
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011987:Receptors, Steroid / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011987:Receptors, Steroid; D000068878:Trastuzumab