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Review
. 2024 Apr 23;31(5):2364-2375.
doi: 10.3390/curroncol31050176.

The Significance of Thyroid Hormone Receptors in Breast Cancer: A Hypothesis-Generating Narrative Review

Trinity Quan  1 , Jessica Cockburn  2 , Sukhbinder Dhesy-Thind  3 , Anita Bane  2 , Hon Leong  4   5 , Christopher Geleff  4 , Catherine Devion  6 , Noor Ajel  1 , Katarzyna J Jerzak  1   6
Affiliations
Review

The Significance of Thyroid Hormone Receptors in Breast Cancer: A Hypothesis-Generating Narrative Review

Trinity Quan et al. Curr Oncol. .

Abstract

Background: Breast cancer (BC) is frequently diagnosed among Canadian women. While targeted therapies are available for most BC patients; treatment resistance is common and novel therapeutic targets are of interest. Thyroid hormones (TH) bound to thyroid hormone receptors (THR) influence cell proliferation and differentiation; they are also involved in the growth and development of normal breast tissue. Evidence suggests that THRβ is a tumor suppressor in various solid tumors.

Purpose: This narrative review discusses retrospective studies regarding the clinical relevance of THRβ as a potential prognostic biomarker and therapeutic target in BC.

Methods: We consulted with an information specialist to develop a search strategy to find all literature related to THRα expression as a potential prognostic and therapeutic biomarker in breast cancer. The primary search was developed for Medline and translated to Embase. The searches were conducted on the Ovid platform on 18 August 2023.

Results: Across seven retrospective studies identified, several have shown an association between higher THRβ1 expression with a lower risk of BC recurrence and with longer overall survival.

Conclusions: Some evidence suggests that THRβ expression is associated with a lower risk of BC recurrence and death. Validation of THRβ as an independent prognostic biomarker and possible predictive biomarker of response to endocrine therapy and/or chemotherapy is of interest. Given that THRβ is upstream of the AKT/PI3K pathway, its potential as a predictive biomarker of response to AKT inhibitors and/or PI3K inhibitors may also be of value. Finally, the potential re-purposing of THRβ agonists as anti-cancer agents warrants investigation.

Keywords: biomarker; breast cancer; thyroid receptor beta.

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Conflict of interest statement

K.J.J.: Consultant/Speaker/Advisory board member—Amgen, AstraZeneca, Apo Biologix, Daiichi Sankyo, Eli Lilly, Esai, Genomic Health, Gilead Sciences, Knight Therapeutics, Merck, Myriad Genetics Inc., Organon, Pfizer, Roche, Seagen, Novartis, Viatris. Research Funding: AstraZeneca, Eli Lilly, Seagen. K.J.J., A.B., S.D.-T., J.C: Patent regarding compounds for treating cancer and methods of use therof (US patent #: 10,576,056; Europe patent #: 3,393,466).

Figures

Figure 1
Figure 1
Chromosome 17 contains the THRA gene encoding THRα1 and THRα2 [4]. THRα2 holds an extra carboxyl-terminal which inhibits T3-mediated signaling and tumor growth [5]. Chromosome 3 contains the THRB gene encoding THRβ1 and THRβ2 [4].
Figure 2
Figure 2
Cytoplasmic signalling pathways of thyroid hormones.
Figure 3
Figure 3
BRCA1 germline mutations association with increased THRβ.
See this image and copyright information in PMC

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