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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

Funding for this study was obtained from the Canadian Association of Medical Oncologists and from the Juravinski Hospital and Cancer Centre Foundation.

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Correspondence to K. J. Jerzak.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Appendix

Appendix

See Table 3.

Table 3 Regression analysis for the exploratory cohort, overall survival outcome

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Jerzak, K.J., Cockburn, J.G., Dhesy-Thind, S.K. et al. Thyroid hormone receptor beta-1 expression in early breast cancer: a validation study. Breast Cancer Res Treat 171, 709–717 (2018). https://doi.org/10.1007/s10549-018-4844-5

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