title: Correlation of mRNA for oestrogen receptor beta splice variants ERbeta1, ERbeta2/ERbetacx and ERbeta5 with outcome in endocrine-treated breast cancer.
abstract: This study has been performed to test the hypothesis that different oestrogen receptor beta (ERbeta) 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 ERbeta1, ERbeta2 and ERbeta5 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, ERalpha, progesterone receptor, Ki67, relapse-free survival (RFS) and overall survival (OS). Seventy per cent of cases were ERbeta1 positive, 69% ERbeta2 positive and 70% ERbeta5 positive. Within the cohort, 47% were positive for all three variants while 10% were negative for all three. ERbeta1 exhibited no discernible relationship with disease outcome. ERbeta2 and ERbeta5 expression was significantly associated with better RFS (P<0.005), and ERbeta2 with better OS (P=0.0002). In multivariate analysis, ERbeta2 (P=0.006), nodal status and the level of Ki67 expression were independent predictors for RFS while ERbeta2 (P=0.0008) and Ki67 status were independent predictors for OS. In the ERalpha-positive cases, or in the subset of those receiving adjuvant tamoxifen, ERbeta2 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 ERbeta are more important assessors than is ERbeta1 alone of the biological status of individual breast cancers, and hence in predicting their response to endocrine therapy.
authors.affiliation: Clatterbridge Cancer Research Trust, J K Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral CH63 4JY, UK. Mike.Davies@ccrt.nhs.uk
authors.forename: M P A
authors.initials: MP
authors.lastname: Davies
authors.forename: P A
authors.initials: PA
authors.lastname: O'Neill
authors.forename: H
authors.initials: H
authors.lastname: Innes
authors.forename: D R
authors.initials: DR
authors.lastname: Sibson
authors.forename: W
authors.initials: W
authors.lastname: Prime
authors.forename: C
authors.initials: C
authors.lastname: Holcombe
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D047629:Estrogen Receptor beta / Q000235:genetics*; D005500:Follow-Up Studies; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047629:Estrogen Receptor beta; D006728:Hormones; D012333:RNA, Messenger