title: Thyroid hormone receptor α in breast cancer: prognostic and therapeutic implications.
abstract: We determined the expression of two transcriptional variants of thyroid hormone receptor alpha (THRα1 and THRα2) in samples from a cohort of breast cancer patients and correlated expression levels with survival. 130 women who were diagnosed with invasive breast carcinoma between 2007 and 2008 were included. Representative sections of their tumours were analyzed in triplicate on a tissue microarray for expression of THRα1 and THRα2 by immunohistochemistry. The prognostic significance of THRα1 and THRα2 expression was assessed using Kaplan-Meier survival analyses, adjusted for known prognostic factors. Seventy-four percent of tumours had high expression of THRα1 (Allred score ≥6) and 40 % had high expression of THRα2. Expression of THRα2 correlated positively with ER expression (p < 0.001) and with PR expression (p < 0.001), but negatively with HER2 expression (p = 0.018). Patients with low THRα2 expression had inferior 5-year overall survival (75.3 %) compared to those with high expression (91.7 %; p = 0.06). In a multivariate model, high THRα2 expression was a significant and independent prognosticator of improved overall survival (HR = 0.84; 95 % CI 0.71-0.98). Many breast tumours express THRα2 at high levels and these patients experience improved survival. Thyroid hormone signalling may be important in a proportion of breast cancers and THRα2 expression may be a regulator of signalling in this pathway.
authors.affiliation: Department of Medicine, University of Toronto, 27 King's College Cir, Toronto, ON, M5S 1A1, Canada.
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Jerzak
authors.forename: Jessica
authors.initials: J
authors.lastname: Cockburn
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Sukhbinder K
authors.initials: SK
authors.lastname: Dhesy-Thind
authors.forename: Anita
authors.initials: A
authors.lastname: Bane
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D015398:Signal Transduction; D037021:Thyroid Hormone Receptors alpha / Q000096:biosynthesis* / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D037021:Thyroid Hormone Receptors alpha; C508053:ERBB2 protein, human