Are Thyroid and Sex Hormone Ratios Predictive of Breast Cancer Risk? A Preliminary Study among A Cohort of Sri Lankan Breast Cancer Patients

Year 2023, , 601 - 607, 31.05.2023

H.m Kasuni Akalanka , Sagarika Ekanayake , Kamani Samarasinghe

https://doi.org/10.30621/jbachs.1078216

Abstract

Purpose: The association of thyroid related diseases and sex hormones with breast cancer (BC) is reported with inconclusive results.
Objectives: The study was designed to analyze the thyroid/sex hormone ratios of BC patients.
Methodology: TSH, T3, T4, estrogen, progesterone and testosterone concentrations of newly diagnosed breast cancer patients (n=155) aged 30 to 75 years and age-matched normal controls (n=75) were analyzed. Thyroid: sex hormone ratios were calculated. Data on history of thyroid related diseases were collected.
Results and Discussion: History of thyroid related diseases was significantly higher (p<0.05) in breast cancer patients compared to controls. Among the remaining, subclinical hyperthyroidism was found in 14%, but only 7% in healthy women. Significantly higher (p<0.05) mean T3 and T4 values and lower TSH levels were observed in patients with breast cancer when compared to healthy. Serum testosterone was significantly low among BC patients. Considering the thyroid to sex hormones ratios among postmenopausal women, T3/testosterone, T4/testosterone, T3/estrogen, T4/ estrogen, ratios were significantly different compared to healthy and the highest significance was found with T3/testosterone. Cutoff values studied from receiver operative characteristic curves indicated that a woman having T3/testosterone above 7.47 showed 12.5 times odds (p=0.000) of being diagnosed with BC.
Conclusion: The present study concludes that the incidence of thyroid related diseases is higher among Sri Lankan BC patients and elevation ofT3/testosterone ratio is indicative of BC

Keywords

Breast cancer, Thyroid hormones, sex hormones

Supporting Institution

University of Sri Jayewardenepura, Sri Lanka

Project Number

ASP/06/RE/MED/2012/20, asp/06/re/med/2013/30

References

• 1. Rasool M.,Naseer MI,Zaigham K, Malik A, Riaz N, ALAM R et al. Comparative study of alterations in tri-iodothyronine (T3) and thyroxine (T4) hormone levels in breast and ovarian cancer. Pak J Med Sci 2014; 30(6): 1356–60.
• 2. Kuijpens JLP, Nyklictek I, Louwman MWJ, Weetman TAP, Pop VJM et al. Hypothyroidism might be related to breast cancer in post-menopausal women.Thyroid; 2005; 15(11): 1253–59.
• 3. Saraiva PP,Padovani CR, Brentani MM, Nogueira C.R Profile of thyroid hormones in breast cancer patients. Braz J Med Biol Res; 2005; 38(5); 761–5.
• 4. Ditsch N, Liebhardt S, Von KF, Lenhard M, Vogeser M, Stitzweg C et al.‘Thyroid Function in Breast Cancer Patients. Anticancer Research,2010; 1718(30):1713–17.
• 5. Tosovic A, Bondeson AG, Bondeson L, Ericsson UB, Malam J, Manjer J, Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women. BCR, 2010; 12(3): R33.
• 6. Tosovic A, Bondeson AG, Bondeson L, Ericsson UB, Manjer J ,T3 levels in relation to prognostic factors in breast cancer: A population-based prospective cohort study. BMC Cancer, 2014; 514-36.
• 7. Mourouzis I, Tzovaras A, Armonis B, Ardavanis A, Skondra M, Misitziz J et al. ‘Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated?. Int J Endocrinol , 2015; 1–6.
• 8. Rose, D. P. and Davis, T. E. Plasma triiodothyronine concentrations in breast cancer. Cancer, 1979; 43(4):1434–38.
• 9. Conde I, Paniagua R, Zamora J, Blanquez MJ, Fraile B, Ruiz A et al ;Influence of thyroid hormone receptors on breast cancer cell proliferation. Annals of oncology, 2006;17(1): 60–4.
• 10. Hercbergs, A. H., Ashur-Fabian, O. and Garfield, D.,Thyroid hormones and cancer: clinical studies of hypothyroidism in oncology. Curr opin endocrinol Diabetes Obes, 2010;17(5) : 432–6.
• 11. Hall LC, Salazar EP, Kane SR, Liu N , Effects of thyroid hormones on human breast cancer cell proliferation. J steroid biochem Mol Biol ,2008; 57–66.
• 12. Akalanka H.M.K , Ekanayake S, Samarasighe K, Serum sex hormone levels and hormone receptor status in identifying breast cancer risk in women’, Indian J Cancer, 2021; "ïn press" doi: 10.4103/ijc.IJC.
• 13. Bolander, F. F. and Topper, Y. J.,Stimulation of lactose synthetase activity and casein synthesis in mouse mammary explants by estradiol. Endocrinology. 1980; 106(2):490-95.
• 14. Søgaard M, Farkas DK, Ehrenstein V, Jorgensen JOL, Dekkers OM, Sorensen HT. Hypothyroidism and hyperthyroidism and breast cancer risk: A nationwide cohort study. Eur J of Endocrinol, 2016 ; 409-14.
• 15. Key, T., Sex hormones and risk of breast cancer in premenopausal women: A collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol ,2013;1009- 1019.
• 16. Dimitrakakis C, Zava D, Marinopoulos S, Tsigginou A, Antsaklis A, Glaser R. et al. Low salivary testosterone levels in patients with breast cancer. BMC cancer, 2010; 10(1), 547.
• 17. Akalanka, H. M. K., Ekanayake, S. and Samarasinghe, K.,Could anthropometric and lipid parameters reflect susceptibility to breast cancer? Comparison of newly diagnosed breast cancer and apparently healthy women. Asian Pac J Cancer Prev,2018; 19(9).
• 18. Cohen, D. H. and LeRoith, D. Obesity, type 2 diabetes, and cancer: The insulin and IGF connection. Endocr Relat Cancer. 2012; 19(5), F27-F45.
• 19. Mariash, CN, Kaiser FE, Schwartz H.L, Towle H.C, Oppenheimer JH, Synergism of thyroid hormone and high carbohydrate diet in the induction of lipogenic enzymes in the rat. Mechanisms and implications. Clin Invest .1980; 65(5): 1126- 34.
• 20. Bisschop PH, Toorians AW, Edert E, Wiersinga WM, Gooren LJ, Fliers E, The effects of sex-steroid administration on the pituitary-thyroid axis in transsexuals. Eur J Endocrinol,2006; 155(1):11-16.
• 21. Maran, R. R. M., Arunakaran, J. and Aruldhas, M. M. T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro. Endocr J, 2000; 47(4): 417-28. 22. Kazanavicius G, Purtokaite LI, Kozloviene D, Kruminis V, Kreivaitiene E. Effect of triiodothyronine on hyperandrogenism in women 2013. Thyroid Res .2013: 6 (Suppl 2):A27.
• 23. Trainor, B. C. and Marler, C. A.Testosterone promotes paternal behaviour in a monogamous mammal via conversion to oestrogen’, Proceedings of the Royal Society B: Biological Sciences.2002; 269, 823-29.