title: Increased mortality in HER2 positive, oestrogen receptor positive invasive breast cancer: a population-based study.
abstract: BACKGROUND
  This study assessed the impact of human epidermal growth factor receptor 2 (HER2) status on the outcomes in an unselected population of breast cancer patients who did not receive HER2-targeted therapy.
  
  
  METHODS
  HER2 status by immunohistochemistry and fluorescence in situ hybridisation was compared with clinicopathological data, overall survival (OS) and disease-free survival (DFS) for all patients presenting with breast cancer over 3 years.
  
  
  RESULTS
  In 865 patients (median follow up 6.02 years), HER2 positivity was identified in 13.3% of all cancers and was associated with higher tumour grade (P<10(-8)), lymphovascular invasion (P<0.001) and axillary nodal metastasis (P=0.003). There was a negative association with oestrogen-receptor (ER) and progesterone-receptor expression (P<10(-8)), but the majority (57%) of HER2+tumours were ER+HER2 positivity was associated with poorer OS (P=0.0046) and DFS (P=0.0001) confined to the lymph node-positive (LN+) and ER+ subgroups.
  
  
  CONCLUSIONS
  HER2-positive cancers were less common in this population-based cohort than most selected series. The association of HER2 positivity with poor prognosis was confined to the ER+ and LN+ subgroups. The survival deficit for the 7.5% of patients with ER+/HER2+ cancer compared with ER+/HER2- patients points to a significant subgroup of women who may not (currently) be considered for HER2-directed therapy.
authors.affiliation: Department of Pathology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. colin.purdie@nhs.net
authors.forename: C A
authors.initials: CA
authors.lastname: Purdie
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: A
authors.initials: A
authors.lastname: Ashfield
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.forename: L B
authors.initials: LB
authors.lastname: Jordan
authors.forename: P
authors.initials: P
authors.lastname: Quinlan
authors.forename: D J A
authors.initials: DJ
authors.lastname: Adamson
authors.forename: J A
authors.initials: JA
authors.lastname: Dewar
authors.forename: A M
authors.initials: AM
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen