Purpose: Preliminary data suggest that high expression of the TRβ1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings.
Methods: In this prospective cohort study, we analyzed the prognostic significance of TRβ1 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 9.6 years (range 0.1-21 years).
Results: High TRβ1 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.
Conclusions: High expression of TRβ1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TRβ expression is associated with chemotherapy resistance in-vitro, TRβ1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TRβ agonists.
Keywords: Biomarkers; Breast neoplasms; Thyroid hormone receptor; Tumor suppressor proteins.