title: The clinical prognostic value of molecular intrinsic tumor subtypes in older breast cancer patients: A FOCUS study analysis.
abstract: BACKGROUND
  It was recently proposed that the molecular breast tumor subtypes are differently distributed in the elderly breast cancer patients, and also lack prognostic value. Given the limited number of elderly patients in previous studies, the aim of this study was to determine the prognostic effect of the molecular intrinsic subtypes in a large older breast cancer population.
  
  
  METHODS
  Older breast cancer patients with invasive, non-metastatic breast cancer with tumor material available for immunohistochemical determination of Ki67, EGFR, CK5/6 and HER-2 were included. ER and PR expression was retrieved from the pathology report. Molecular subtypes were: Luminal A, Luminal B, ERBB2, Basal-like and Unclassified. Primary endpoint was Relapse Free Period (RFP), taking into account the competing risk of mortality, and adjusted for the most important patient, tumor and treatment characteristics. Secondary endpoint was Relative Survival (RS).
  
  
  RESULTS
  Overall, 1362 patients were included. Patients with a Luminal A subtype had the lowest risk of recurrence (11% at 5 yrs). Patients with a Basal (24% at 5yrs) or ERBB2 (34% at 5yrs) molecular breast tumor subtype had the highest risk of recurrence. The ERBB2 subtype had the worst prognosis in terms of RFP (SHR 2.07, 95% CI 1.35-3.20; p = 0.001). The worst RS was again observed for the ERBB2 subtype (48% at 10 yrs). In multivariable analyses, the relative excess risk of death for all molecular subtypes was significantly worse compared to the Luminal A subtype.
  
  
  CONCLUSIONS
  Molecular intrinsic breast tumor subtypes have significant prognostic value in the elderly population, even after taking competing mortality into account.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Charla C
authors.initials: CC
authors.lastname: Engels
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mandy
authors.initials: M
authors.lastname: Kiderlen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Antien L
authors.initials: AL
authors.lastname: Mooyaart
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Vlierberghe
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.j.liefers@lumc.nl.
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: Breast cancer; Clinical outcome; Competing mortality; Elderly; Molecular subtypes; Prognostication