title: Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53.
abstract: BACKGROUND
  The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC.
  
  
  METHODS
  The ER+ tumours were classified as 'luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or 'luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS).
  
  
  RESULTS
  In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR.
  
  
  CONCLUSIONS
  The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. e.millar@garvan.org.au
authors.forename: E K A
authors.initials: EK
authors.lastname: Millar
authors.forename: P H
authors.initials: PH
authors.lastname: Graham
authors.forename: C M
authors.initials: CM
authors.lastname: McNeil
authors.forename: L
authors.initials: L
authors.lastname: Browne
authors.forename: S A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: A
authors.initials: A
authors.lastname: Boulghourjian
authors.forename: J H
authors.initials: JH
authors.lastname: Kearsley
authors.forename: G
authors.initials: G
authors.lastname: Papadatos
authors.forename: G
authors.initials: G
authors.lastname: Delaney
authors.forename: C
authors.initials: C
authors.lastname: Fox
authors.forename: E
authors.initials: E
authors.lastname: Nasser
authors.forename: A
authors.initials: A
authors.lastname: Capp
authors.forename: R L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015412:Mastectomy, Segmental; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D020266:Radiotherapy, Conformal; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53