The Role of Thyroid Disease and Other Biomarkers in Invasive Breast Cancer: A 3-year Retrospective Comparative Study

Alexandrina Nikova; Spyridon Plakas; Vasilios Tselepidis; Pinelopi Vlotinou; Helena Michalopoulou; Anna Tsiakiri; Loukas Karelis; Christos Valavanis; Eustathios Vlachakis; Maria Kyriazi

doi:10.2478/fco-2024-0026

.blurhash-client-img { display: none !important; }

The Role of Thyroid Disease and Other Biomarkers in Invasive Breast Cancer: A 3-year Retrospective Comparative Study

Forum of Clinical Oncology

AHEAD OF PRINT

By: Alexandrina Nikova, Spyridon Plakas, Vasilios Tselepidis, Pinelopi Vlotinou, Helena Michalopoulou, Anna Tsiakiri, Loukas Karelis, Christos Valavanis, Eustathios Vlachakis and Maria Kyriazi

Open Access

|Jul 2026

Abstract

Objective

Breast cancer (BC) is the leading cause of cancer-related death among women. Among various prognostic systems, molecular subtypes represent one of the most recent advancements. Recent studies suggest that thyroid disease may be a favorable prognostic factor in BC and thyroid hormones might influence disease progression. However, thyroid-stimulating hormone (TSH) is generally considered unrelated to cancer aggressiveness. This study aimed to examine the postoperative TSH levels and evaluate the impact of thyroid disease on cancer aggressiveness.

Methods

A retrospective comparative analysis was conducted on patients with invasive BC treated between 2017 and 2019. Ninety-seven patients were included and divided into two groups: Group A (n = 49), without thyroid disease, and Group B (n = 48), with thyroid disease. Data analysis was performed using Statistical Package for the Social Sciences version 25.

Results

Significant correlations suggested that preoperative calcium levels are linked to cancer aggressiveness and may serve as potential prognostic factors. No differences were found in preoperative and postoperative TSH values between groups. However, a significant correlation was observed between preoperative TSH levels and progesterone receptor status.

Conclusion

Thyroid disease appears to be associated with a more favorable prognosis based on molecular subtype distribution. Future research should investigate the role of TSH and its relationship to overall patient survival.

References

World Health Organization. Breast Cancer. https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/ Available on 24.03.2020
Search in Google Scholar Back to article
Ferlay, J., Soerjomataram, I., Dikshit, R. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386
Search in Google Scholar Back to article
Hoon Tan P¹, Ellis I², Allison K³, Brogi E⁴, Fox SB⁵, Lakhani S⁶, Lazar AJ⁷, Morris EA⁴, Sahin A⁷, Salgado R⁸, Sapino A^9,10, Sasano H¹¹, Schnitt S¹², Sotiriou C¹³, van Diest P¹⁴, White VA¹⁵, Lokuhetty D¹⁵, Cree IA¹⁵; WHO Classification of Tumours Editorial Board. The 2019 WHO classification of tumours of the breast. Histopathology. 2020
Search in Google Scholar Back to article
Agarwal I. Blanco L. WHO classification of breast tumors. 2020 https://www.pathologyoutlines.com/topic/breastmalignantwhoclassification.html
Search in Google Scholar Back to article
Perou CM, Sorlie T, Eisen MB, Rijn M van de, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000;406:747–52.
Search in Google Scholar Back to article
Fragomeni SM, Sciallis A, Jeruss JS. Molecular Subtypes and Local-Regional Control of Breast Cancer. Surg Oncol Clin N Am. 2018;27(1):95–120.
Search in Google Scholar Back to article
Fallahpour S, Navaneelan T, De P, Borgo A. Breast cancer survival by molecular subtype: a population-based analysis of cancer registry data. CMAJ Open. 2017;5(3):E734–E739.
Search in Google Scholar Back to article
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–182
Search in Google Scholar Back to article
Hercbergs A, Mousa SA, Leinung M, Lin HY, Davis PJ. Thyroid Hormone in the Clinic and Breast Cancer. Horm Cancer. 2018;9(3):139–143. doi:10.1007/s12672-018-0326-9
Open DOI Search in Google Scholar Back to article
Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010 Oct 20;304(15):1684–92
Search in Google Scholar Back to article
Villa NM, Li N, Yeh MW, Hurvitz SA, Dawson NA, Leung AM. SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS. Endocr Pract. 2015;21(9):1040–1045.
Search in Google Scholar Back to article
American Cancer Society. Breast Cancer Facts & Figures 2019–2020. Atlanta: American Cancer Society, Inc. 2019
Search in Google Scholar Back to article
Mehrgou A, Akouchekian M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J Islam Repub Iran. 2016;30:369.
Search in Google Scholar Back to article
Armaou S, Pertesi M, Fostira F, Thodi G, Athanasopoulos PS, Kamakari S. et al. Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases. Br J cancer. 2009;101(1):32–7
Search in Google Scholar Back to article
Calderon-Garciduenas AL, Ruiz-Flores P, Cerda-Flores RM, Barrera-Saldana HA. Clinical follow up of mexican women with early onset of breast cancer and mutations in the BRCA1 and BRCA2 genes. Salud publica de Mexico. 2005;47(2):110–5
Search in Google Scholar Back to article
Tereschenko IV, Basham VM, Ponder BA, Pharoah PD. BRCA1 and BRCA2 mutations in Russian familial breast cancer. Human mutation. 2002;19(2):184
Search in Google Scholar Back to article
Ayub SG, Rasool S, Ayub T, Khan SN, Wani KA, Andrabi KI. Mutational analysis of the BRCA2 gene in breast carcinoma patients of Kashmiri descent. Mol Med Reports. 2014;9(2):749–53.
Search in Google Scholar Back to article
Balraj P, Khoo AS, Volpi L, Tan JA, Nair S, Abdullah H. Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients. Singapore Med J. 2002;43(4):194–7.
Search in Google Scholar Back to article
Musolino A, Naldi N, Michiara M, Bella MA, Zanelli P, Bortesi B. et al. A breast cancer patient from Italy with germline mutations in both the BRCA1 and BRCA2 genes. Breast cancer res treat. 2005;91(2):203–5
Search in Google Scholar Back to article
Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L. et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol. 2002;20(9):2310–8.
Search in Google Scholar Back to article
Phillips KA. Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers. J Clin Oncol. 2000;18(21 Suppl):107s–12s.
Search in Google Scholar Back to article
Pylkas K, Erkko H, Nikkila J, Solyom S, Winqvist R. Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families. BMC cancer. 2008;8:146.
Search in Google Scholar Back to article
Loboda AP, Adonin LS, Zvereva SD, et al. BRCA Mutations-The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers. Int J Mol Sci. 2023;24(5):4982.
Search in Google Scholar Back to article
Dutil J, Colon-Colon JL, Matta JL, Sutphen R, Echenique M. Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico. Cancer genetics. 2012;205(5):242–8.
Search in Google Scholar Back to article
Makki J. Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance. Clin Med Insights Pathol. 2015;8:23–31
Search in Google Scholar Back to article
Wang, J., Li, B., Luo, M. et al. Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance. Sig Transduct Target Ther 9, 83 (2024). https://doi.org/10.1038/s41392-024-01779-3
Search in Google Scholar Back to article
Toikkanen S, Pylkkänen L, Joensuu H. Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma. Br J Cancer. 1997;76(9):1234–1240.
Search in Google Scholar Back to article
Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736–1747. doi:10.1093/annonc/mdr304
Open DOI Search in Google Scholar Back to article
Harbeck N, Thomssen C, Gnant M. St. Gallen 2013: brief preliminary summary of the consensus discussion. Breast Care (Basel). 2013;8(2):102–109.
Search in Google Scholar Back to article
Balic M, Thomssen Ch, Wuerstlein R, Gnant M, Harbeck N. St. Gallen/Vienna 2019: A Brief Summary of the Consensus Discussion on the Optimal Primary Breast Cancer Treatment. Breast care. 2019; 14: 103–110
Search in Google Scholar Back to article
He L, Lv Y, Song Y, Zhang B. The prognosis comparison of different molecular subtypes of breast tumors after radiotherapy and the intrinsic reasons for their distinct radiosensitivity. Cancer Manag Res. 2019;11:5765–5775
Search in Google Scholar Back to article
Rubin E, Shan KS, Dalal S, Vu DUD, Milillo-Naraine AM, Guaqueta D, Ergle A. Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers. International Journal of Molecular Sciences. 2024; 25(2):1064. https://doi.org/10.3390/ijms25021064
Search in Google Scholar Back to article
Iqbal N, Iqbal N. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;2014:852748.
Search in Google Scholar Back to article
Björnström L¹, Sjöberg M. Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes. Mol Endocrinol. 2005 Apr;19(4):833–42
Search in Google Scholar Back to article
Lu Q¹, Pallas DC, Surks HK, Baur WE, Mendelsohn ME, Karas RH. Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor α. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17126–31
Search in Google Scholar Back to article
Chen P, Li B, Ou-Yang L. Role of estrogen receptors in health and disease. Front Endocrinol (Lausanne). 2022;13:839005. Published 2022 Aug 18. doi:10.3389/fendo.2022.839005.
Open DOI Search in Google Scholar Back to article
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C, Godwin J, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784.
Search in Google Scholar Back to article
Song F, Zhang J, Li S, et al. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy. Onco Targets Ther. 2017;10:4859–4867.
Search in Google Scholar Back to article
Yao N, Song Z, Wang X, Yang S, Song H. Prognostic Impact of Progesterone Receptor Status in Chinese Estrogen Receptor Positive Invasive Breast Cancer Patients. J Breast Cancer. 2017;20(2):160–169.
Search in Google Scholar Back to article
Li Z, Wei H, Li S, Wu P, Mao X. The Role of Progesterone Receptors in Breast Cancer. Drug Des Devel Ther. 2022;16:305–314. Published 2022 Jan 26. doi:10.2147/DDDT.S336643
Open DOI Search in Google Scholar Back to article
Scholzen T, Gerdes J (March 2000). “The Ki-67 protein: from the known and the unknown”. J Cell Phys. 182 (3): 311–22
Search in Google Scholar Back to article
Soliman NA, Yussif SM. Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med. 2016;13(4):496–504.
Search in Google Scholar Back to article
Inwald EC, Klinkhammer-Schalke M, Hofstädter F, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139(2):539–552.
Search in Google Scholar Back to article
Davey MG, Hynes SO, Kerin MJ, Miller N, Lowery AJ. Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer. Cancers (Basel). 2021;13(17):4455. Published 2021 Sep 3. doi:10.3390/cancers13174455.
Open DOI Search in Google Scholar Back to article
Fariduddin MM, Haq N, Bansal N. Hypothyroid Myopathy. [Updated 2024 Jun 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519513/
Search in Google Scholar Back to article
Sogaard M, Farkas DK, Ehrenstein V, Jorgensen JO, Dekkers OM, Sorensen HT. Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study. Eur J Endocrinol. 2016;174(4):409–414.
Search in Google Scholar Back to article
Tang HY, Lin HY, Zhang S, Davis FB, Davis PJ. Thyroid Hormone Causes Mitogen-Activated Protein Kinase-Dependent Phosphorylation of the Nuclear Estrogen Receptor. Endocrinology 145(7):3265–3272
Search in Google Scholar Back to article
Falstie-Jensen, A.M., Kjærsgaard, A., Lorenzen, E.L. et al. Hypothyroidism and the risk of breast cancer recurrence and all-cause mortality - a Danish population-based study. Breast Cancer Res 21, 44 (2019).
Search in Google Scholar Back to article
Ortega-Olvera, C., Ulloa-Aguirre, A., Ángeles-Llerenas, A. et al. Thyroid hormones and breast cancer association according to menopausal status and body mass index. Breast Cancer Res 20, 94 (2018).
Search in Google Scholar Back to article
So CL, Saunus JM, Roberts-Thomson SJ, Monteith GR. Calcium signalling and breast cancer. Semin Cell Dev Biol. 2019;94:74–83. doi:10.1016/j.semcdb.2018.11.001
Open DOI Search in Google Scholar Back to article
Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States) Cancer Causes Control. 2005;16:83–95
Search in Google Scholar Back to article
Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol. 2017;453:36–45. doi:10.1016/j.mce.2017.04.008.
Open DOI Search in Google Scholar Back to article
Almquist M, Manjer J, Bondeson L, Bondeson AG. Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women. Cancer Causes Control. 2007;18:595–602
Search in Google Scholar Back to article
Sprague BL, Skinner HG, Trentham-Dietz A, Lee KE, Klein BE, Klein R. Serum calcium and breast cancer risk in a prospective cohort study. Ann Epidemiol. 2010;20(1):82–85.
Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.2478/fco-2024-0026 | Journal eISSN: 1792-362X | Journal ISSN: 1792-345X

Journal RSS Feed

Language: English

Submitted on: Dec 25, 2024

Accepted on: Aug 27, 2025

Published on: Jul 8, 2026

Published by: Helenic Society of Medical Oncology

In partnership with: Paradigm Publishing Services

Keywords:

thyroid disease,

breast cancer,

thyroid hormones,

Tumor Nodes Metastasis,

Related subjects:

Haematology, oncology

© 2026 Alexandrina Nikova, Spyridon Plakas, Vasilios Tselepidis, Pinelopi Vlotinou, Helena Michalopoulou, Anna Tsiakiri, Loukas Karelis, Christos Valavanis, Eustathios Vlachakis, Maria Kyriazi, published by Helenic Society of Medical Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

AHEAD OF PRINT