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M Dillon, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Irealnd, Dublin, Ireland
A Stafford, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons, Dublin, Ireland
G Kelly, School of Mathematical Sciences and Actuarial Science, University College Dublin, Dublin, Ireland
A Redmond, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Irealnd, Dublin, Ireland
M McIlroy, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Irealnd, Dublin, Ireland
T Crotty, School of Medicine and Medical Science, St Vincent's University Hospital, University College Dublin, Dublin, Ireland
E McDermott, School of Medicine and Medical Science, St Vincent's University Hospital, University College Dublin, Dublin, Ireland
A Hill, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Irealnd, Dublin, Ireland
l Young, Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin , Ireland

Correspondence: Ls Young, Email: lyoung{at}rcsi.ie

Abstract

COX-2 is associated with breast tumour progression. Clinical and molecular studies implicate HER2 in the regulation of COX-2 expression. Recent reports raise the possibility that HER2 could mediate these effects through direct transcriptional mechanisms. The relationship between HER2 and COX-2 was investigated in a cohort of breast cancer patients with or without endocrine treatment. A tissue microarray comprising of tumours from 560 patients with 10 years follow-up was analysed for HER2, ERK1/2, PEA3 and COX-2 expression. Subcellular localisation of HER2 was assessed by immunofluorescence and confocal microscopy. Expression of markers examined was analysed in relation to classic clincopathological parameters and disease free survival in the presence and absence of tamoxifen. COX-2 expression associated with both membranous and nuclear expression of HER2 (p=0.0033 and p<0.00001, respectively). No association was detected between COX-2 and either ERK1/2 or PEA3 (p=0.7 and p=0.3, respectively). None of the markers were found to be independently prognostic. Membrane HER2, nuclear HER2 and COX-2 however were all found to predict poor disease free survival in patients on endocrine treatment (p=0.0017, p=0.0003 and p=0.0202, respectively). Moreover patients who were positive for COX-2 predicted adverse effects of tamoxifen (p=0.0427). These clinical ex-vivo data are consistent with molecular observations that HER2 can regulate COX-2 expression through direct transcriptional mechanisms. COX-2 expression correlates with disease progression on endocrine treatment. This study supports a role for COX-2 as a predictor of adverse effects of tamoxifen in breast cancer patients.