• T M A Abdel-Fatah, S E B McArdle, C Johnson, P M Moseley, G R Ball, A G Pockley, I O Ellis, R C Rees, and S Y T Chan.
• Department of Clinical Oncology, University of Nottingham City Hospital NHS Trust, Nottingham, UK.
• Br. J. Cancer. 2014 May 13; 110 (10): 2450-61.

BackgroundHAGE protein is a known immunogenic cancer-specific antigen.MethodsThe biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.ResultsEight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003).ConclusionsThis is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC.

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