title: Age related influence of triple receptor status on metastatic breast cancer post relapse survival.
abstract: OBJECTIVE
  Prognostic factors in metastatic breast cancer (MBC) differ from those of primary breast cancer. The aim of this study was to identify the clinical significance of combined estrogen and progesterone receptors (ER,PR) and human epidermal growth factor receptor-2 (HER2) status on MBC post relapse survival.
  
  
  METHODS
  The survival of 109 MBC patients was analyzed according to clinical characteristics and ER/PR status (tested by ligand binding assay) and HER2 status (tested by chromogenic in situ hybridization/CISH).
  
  
  RESULTS
  Proper parameters for follow up of MBC patients were patient age, duration of disease free interval (DFI), dominant site of metastasis, number of metastatic sites and ER, PR status. Follow up of MBC patients showed the statistically significant difference in post relapse survival between patients with extreme phenotypes ER+PR+ and ER-PR-. Addition of HER2 status confirmed negative effect of HER2 amplification on MBC post relapse survival resulting in worse prognosis of ER-PR-HER2+ patients. The corresponding triple receptor (ER,PR,HER2) combination repeated the same pattern. In combination with patient age it was shown that difference in post relapse survival between extreme phenotypes (ER+PR+HER2- and ER-PRHER2+) was age related i.e. patients older than 50 years, with ER-PR-HER2+ phenotype, had mortality rate 100% and median survival time 14 months.
  
  
  CONCLUSIONS
  There is a strong indication for use of combined triple receptor status for follow-up of MBC patients. Based on our results, the worst phenotype was neither triple positive nor triple negative, but the one that most likely reflects the biological background of these biomarkers (ERPR- HER2+). Double and triple receptor status showed repeated pattern of influence on prognosis, but the finding that ER-PR-HER2+ phenotype in an age-restricted subgroup of patients means extremely poor prognosis and a highest mortality rate deserves further consideration regarding therapy efficiency.
authors.affiliation: Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Todorovic-Rakovic
authors.forename: Z
authors.initials: Z
authors.lastname: Neskovic-Konstantinovic
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human