Correlation of mRNA for oestrogen receptor beta splice variants ERβ1, ERβ2/ERβcx and ERβ5 with outcome in endocrine-treated breast cancer

Abstract

This study has been performed to test the hypothesis that different oestrogen receptor beta (ERβ) 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 ERβ1, ERβ2 and ERβ5 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, ERα, progesterone receptor, Ki67, relapse-free survival (RFS) and overall survival (OS). Seventy per cent of cases were ERβ1 positive, 69% ERβ2 positive and 70% ERβ5 positive. Within the cohort, 47% were positive for all three variants while 10% were negative for all three. ERβ1 exhibited no discernible relationship with disease outcome. ERβ2 and ERβ5 expression was significantly associated with better RFS (P<0.005), and ERβ2 with better OS (P=0.0002). In multivariate analysis, ERβ2 (P=0.006), nodal status and the level of Ki67 expression were independent predictors for RFS while ERβ2 (P=0.0008) and Ki67 status were independent predictors for OS. In the ERα-positive cases, or in the subset of those receiving adjuvant tamoxifen, ERβ2 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 ERβ are more important assessors than is ERβ1 alone of the biological status of individual breast cancers, and hence in predicting their response to endocrine therapy.