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Clatterbridge Cancer Research Trust, J K Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral CH63 4JY, UK
¹ Cancer Tissue Bank Research Centre, University of Liverpool, Liverpool L69 3GA, UK
² Breast Services, Linda McCartney Centre, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK
³ Department of Cellular and Molecular Pathology, University of Liverpool, Liverpool L69 3GA, UK

(Requests for offprints should be addressed to M P A Davies; Email: Mike.Davies{at}ccrt.nhs.uk)

This study has been performed to test the hypothesis that different oestrogen receptor beta (ERß) splice variants may be important determinants of clinical parameters, including outcome, in post-menopausal women with breast cancer receiving adjuvant endocrine treatment but no chemotherapy. Splice variants ERß1, ERß2 and ERß5 have been analysed by semi-quantitative RT-PCR in a cohort of 105 patients with primary breast cancer. Clinical correlates included age, grade, size, nodal status, ER, progesterone receptor, Ki67, relapse-free survival (RFS) and overall survival (OS). Seventy per cent of cases were ERß1 positive, 69% ERß2 positive and 70% ERß5 positive. Within the cohort, 47% were positive for all three variants while 10% were negative for all three. ERß1 exhibited no discernible relationship with disease outcome. ERß2 and ERß5 expression was significantly associated with better RFS (P<0.005), and ERß2 with better OS (P=0.0002). In multivariate analysis, ERß2 (P=0.006), nodal status and the level of Ki67 expression were independent predictors for RFS while ERß2 (P=0.0008) and Ki67 status were independent predictors for OS. In the ER-positive cases, or in the subset of those receiving adjuvant tamoxifen, ERß2 was significantly associated with good RFS (P<0.0005) and was the only independent marker of OS. We conclude that precise identification of splice variants of ERß are more important assessors than is ERß1 alone of the biological status of individual breast cancers, and hence in predicting their response to endocrine therapy.

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