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Peer-reviewedCC BYMedicine

Association between thyroid hormone sensitivity indices and surrogate clinicopathologic subtypes of breast cancer : A retrospective single-center study

  • Mehmet Mert Hidiroglu1
  • Sevket Baris Morkavuk2
  • Safak Akin3
  • Ibrahim Burak Bahcecioglu2
  • Nese Ersoz Gulcelik3
  • Mehmet Ali Gulcelik2
  1. 1Department of General Surgery, Health Sciences University, Faculty of Medicine, Gülhane Research and Training Hospital, Ankara, Turkey
  2. 2Department of Surgical Oncology, Health Sciences University, Faculty of Medicine, Gülhane Research and Training Hospital, Ankara, Turkey
  3. 3Department of Endocrinology and Metabolism, Health Sciences University, Faculty of Medicine, Gülhane Research and Training Hospital, Ankara, Turkey.
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Abstract

Despite advances in screening and treatment for breast cancer and a substantial decline in the disease’s mortality, breast cancer continues to show increased incidence and remains a major global health burden. A major factor in these trends is breast cancer’s heterogeneity, as reflected by distinct subtypes. Central thyroid hormone sensitivity can be assessed using the thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone (TSH) index (TSHI), TSH T4 resistance index (TT4RI), and the free triiodothyronine/free thyroxine (fT3/fT4) ratio, an indirect proxy of peripheral thyroid hormone conversion. We investigated associations between surrogate clinicopathologic subtypes of breast cancer and central thyroid hormone sensitivity indices and the fT3/fT4 ratio. We retrospectively analyzed 109 patients with preoperative thyroid function tests who underwent surgery for breast cancer between 2017 and 2022 at Gülhane Training and Research Hospital, Department of Surgical Oncology. We investigated associations of surrogate clinicopathologic subtypes with TFQI, TT4RI, TSHI, and the fT3/fT4 ratio. Associations with receptor and Ki-67 status were additionally evaluated using separate age- and BMI-adjusted Firth’s penalized logistic regression models, each including 1 thyroid index. No statistically significant differences emerged in the distribution of central thyroid hormone sensitivity indices across surrogate clinicopathologic subtypes (P = .349 for TFQI, P = .867 for TT4RI, P = .645 for TSHI). The fT3/fT4 ratio differed significantly across subtypes (P < .001). In separate age- and BMI-adjusted Firth’s models, a higher fT3/fT4 ratio was associated with lower odds of HER2 positivity (adjusted OR = 0.226, 95% CI: 0.088–0.579; P = .002) but higher odds of being in the high Ki-67 group (adjusted OR = 2.096, 95% CI: 1.219–3.603; P = .007). No statistically significant associations were observed between these outcomes and central thyroid hormone sensitivity indices. The fT3/fT4 ratio differed significantly across breast cancer subtypes, with higher values in the triple-negative breast cancer group than in several other subtypes, whereas central thyroid hormone sensitivity indices showed no significant differences. These findings suggest a possible association between peripheral thyroid hormone conversion and clinicopathologic tumor phenotype.

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Cite

BibTeXRIS
BibTeX
@article{hidiroglu2026association,
  title = {{Association between thyroid hormone sensitivity indices and surrogate clinicopathologic subtypes of breast cancer : A retrospective single-center study}},
  author = {Mehmet Mert Hidiroglu and Sevket Baris Morkavuk and Safak Akin and Ibrahim Burak Bahcecioglu and Nese Ersoz Gulcelik and Mehmet Ali Gulcelik},
  journal = {Medicine},
  year = {2026},
  month = oct,
  doi = {10.1097/md.0000000000051340},
  url = {https://europepmc.org/article/PMC/PMC13727159},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Association between thyroid hormone sensitivity indices and surrogate clinicopathologic subtypes of breast cancer : A retrospective single-center study
AU  - Mehmet Mert Hidiroglu
AU  - Sevket Baris Morkavuk
AU  - Safak Akin
AU  - Ibrahim Burak Bahcecioglu
AU  - Nese Ersoz Gulcelik
AU  - Mehmet Ali Gulcelik
PY  - 2026
DA  - 2026/10/30
JO  - Medicine
DO  - 10.1097/md.0000000000051340
UR  - https://europepmc.org/article/PMC/PMC13727159
AB  - Despite advances in screening and treatment for breast cancer and a substantial decline in the disease’s mortality, breast cancer continues to show increased incidence and remains a major global health burden. A major factor in these trends is breast cancer’s heterogeneity, as reflected by distinct subtypes. Central thyroid hormone sensitivity can be assessed using the thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone (TSH) index (TSHI), TSH T4 resistance index (TT4RI), and the free triiodothyronine/free thyroxine (fT3/fT4) ratio, an indirect proxy of peripheral thyroid hormone conversion. We investigated associations between surrogate clinicopathologic subtypes of breast cancer and central thyroid hormone sensitivity indices and the fT3/fT4 ratio. We retrospectively analyzed 109 patients with preoperative thyroid function tests who underwent surgery for breast cancer between 2017 and 2022 at Gülhane Training and Research Hospital, Department of Surgical Oncology. We investigated associations of surrogate clinicopathologic subtypes with TFQI, TT4RI, TSHI, and the fT3/fT4 ratio. Associations with receptor and Ki-67 status were additionally evaluated using separate age- and BMI-adjusted Firth’s penalized logistic regression models, each including 1 thyroid index. No statistically significant differences emerged in the distribution of central thyroid hormone sensitivity indices across surrogate clinicopathologic subtypes (P = .349 for TFQI, P = .867 for TT4RI, P = .645 for TSHI). The fT3/fT4 ratio differed significantly across subtypes (P < .001). In separate age- and BMI-adjusted Firth’s models, a higher fT3/fT4 ratio was associated with lower odds of HER2 positivity (adjusted OR = 0.226, 95% CI: 0.088–0.579; P = .002) but higher odds of being in the high Ki-67 group (adjusted OR = 2.096, 95% CI: 1.219–3.603; P = .007). No statistically significant associations were observed between these outcomes and central thyroid hormone sensitivity indices. The fT3/fT4 ratio differed significantly across breast cancer subtypes, with higher values in the triple-negative breast cancer group than in several other subtypes, whereas central thyroid hormone sensitivity indices showed no significant differences. These findings suggest a possible association between peripheral thyroid hormone conversion and clinicopathologic tumor phenotype.
SN  - 0304-5412
SN  - 1536-5964
SN  - 0025-7974
ER  -