Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53

Br J Cancer. 2011 Jul 12;105(2):272-80. doi: 10.1038/bjc.2011.228. Epub 2011 Jun 28.

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.

Conclusion: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma / diagnosis*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism*
  • Ki-67 Antigen / physiology
  • Mastectomy, Segmental
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Radiotherapy, Conformal
  • Randomized Controlled Trials as Topic
  • Receptors, Estrogen / metabolism*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Tumor Suppressor Protein p53