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.
Highlights
The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER þ ) breast cancer after breast-conserving therapy (BCT)
We previously described the clinical usefulness of a five biomarker panel (Millar et al, 2009b; ER, PR, HER2, CK 5/6 and EGFR) and have further defined luminal tumours by including Ki-67 and p53 status, the latter described in higher grade tumours, overexpressed more frequently within luminal B’ (LB) (Sorlie, 2004; Jacquemier et al, 2008; Hugh et al, 2009; Carey, 2010; Weigelt et al, 2010b) and as a predictor of endocrine resistance in some studies (Yamashita et al, 2006)
Having identified differences in Ki67 and p53 in ER þ tumours in our training cohort, we assessed the difference between ER+ and/or PR+ (LA) and B tumours in expression level of these two antigens in our validation cohort (n 1⁄4 498)
Summary
The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER þ ) breast cancer after breast-conserving therapy (BCT). 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. Kaplan – Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasisfree survival (DMFS) and breast cancer-specific survival (BCSS). CONCLUSION: The prognostic evaluation of ER þ 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 þ patients with a greater probability of failure with endocrine therapy. British Journal of Cancer (2011) 105, 272 – 280. doi:10.1038/bjc.2011.228 www.bjcancer.com Published online 28 June 2011 & 2011 Cancer Research UK
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