Thyroid hormone receptor beta-1 expression in early breast cancer: a validation study

PurposePreliminary data suggest that high expression of the TR1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings.MethodsIn this prospective cohort study, we analyzed the prognostic significance of TR1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000. Details regarding patient age at diagnosis, systemic, and local therapies, as well as pathological features of their tumor have been systematically recorded. Clinical outcomes including breast cancer recurrence and death have been updated at least once each year with a median follow-up of 9.6years (range 0.1-21years).ResultsHigh TR1 expression (>4 on the Allred score) was associated with a longer breast cancer-specific survival with a HR 0.45 (95% CI 0.33-0.61), p<0.0001 in a univariable Cox regression model. This was maintained in a multivariable model adjusted for age, tumor size, nodal status, chemotherapy, hormone therapy, radiotherapy, surgery, and ER status with a HR of 0.61 (95% CI 0.44-0.85), p=0.004.ConclusionsHigh expression of TR1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TR expression is associated with chemotherapy resistance in-vitro, TR1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TR agonists.