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Alteration of Thyroid Function in Indian HER 2-Negative Breast Cancer Patients Undergoing Chemotherapy

  • Ashif Khan, Mohd ;
  • Bhurani, Dinesh ;
  • Agarwal, Nidhi B
  • Published : 2015.12.03

Abstract

Background: Thyroid hormones (TH) are regulated by the hypothalamic-pituitary axis, which plays an important role in cell growth, differentiation, development and other aspects of metabolism. It is believed that an active hypothalamic-pituitary axis increases the susceptibility of thyroid dysfunction during systemic chemotherapy. In order to investigate the relation between thyroid function and chemotherapy the present study was designed to investigate TH in breast cancer patients receiving at least three cycles of chemotherapy. The levels of TH were measured at the baseline and before each cycle of chemotherapy. Materials and Methods: Blood samples for estimation of TH levels were collected from 80 (pre-menopausal-40; post-menopausal-40) breast cancer patients just before they were undergoing - $1^{st}$, $2^{nd}$, $3^{rd}$ and $4^{th}$ cycle of chemotherapy. The serum was separated and $T_3$, $T_4$ and TSH levels were determined by chemiluminescence method. Results: $T_3$ and $T_4$ were found significantly decreased and TSH was found significantly increased after $1^{st}$ (p<0.001), $2^{nd}$ (p<0.0001) and $3^{rd}$ cycle of chemotherapy (p<0.0001). The variation of $T_3$ levels (decreased) and TSH levels (increased) was found more in post-menopausal (p<0.0001) women then in pre-menopausal women after $3^{rd}$ cycle of chemotherapy as compared to baseline (p<0.001). Conclusions: TH were remarkably altered after each cycle of chemotherapy leading to decline in thyroid function of breast cancer patients. Further, the results also indicated that post-menopausal women were more prone towards decline in thyroid function then pre-menopausal women. The present study proposes the monitoring of TH after each cycle of chemotherapy in breast cancer patients.

Keywords

Thyroid hormone;chemotherapy;breast cancer;subclinical hypothyroidism;menopause

References

  1. Andersen S, Pedersen KM, Bruun NH, Laurberg P (2002). Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab, 87, 1068-72. https://doi.org/10.1210/jcem.87.3.8165
  2. Aoki Y, Belin RM, Clickner R, et al (2007). Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid, 17, 1211-23. https://doi.org/10.1089/thy.2006.0235
  3. Babu GR, Lakshmi SB, Thiyagarajan JA (2013). Epidemiological correlates of breast cancer in South India. Asian Pac J Cancer Prev, 14, 5077-83. https://doi.org/10.7314/APJCP.2013.14.9.5077
  4. Beex L, Ross A, Smals A, Kloppenborg P (1977). 5-fluorouracil- induced increase of total serum thyroxine and triiodothyronine. Cancer Treat Rep, 61, 1291-5.
  5. Chapman RM (1992). Gonadal toxicity and teratogenicity, In: Perry MC, editors. Chemotherapy Source Book, Williams Wilkins: Baltimore, 710-53.
  6. De Groot S, Janssen LGM, Charehbili A, et al (2015). Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01). Breast Cancer Res Treat, 149, 461-6. https://doi.org/10.1007/s10549-014-3256-4
  7. Del Ghianda S, Tonacchera M, Vitti P (2014). Thyroid and menopause. Climacteric, 17, 225-34. https://doi.org/10.3109/13697137.2013.838554
  8. Dong BJ (2000). How medications affect thyroid function. West J Med, 172, 102-6. https://doi.org/10.1136/ewjm.172.2.102
  9. Ferster A, Glinoer D, Van Vliet G, Otten J (1992). Thyroid function during L-asparaginase therapy in children with acute lymphoblastic leukemia: difference between induction and late intensification. Am J Pediatr Hematol Oncol, 14, 192-6. https://doi.org/10.1097/00043426-199208000-00002
  10. Fujiwara Y, Chayahara N, Mukohara T, et al (2013). Hypothyroidism in patients with colorectal carcinoma treated with fluoropyrimidines. Oncol Rep, 30, 1802-6. https://doi.org/10.3892/or.2013.2644
  11. Garnick MB, Larsen PR (1979). Acute deficiency of thyroxine binding globulin during L-asparaginase therapy. N Engl J Med, 301, 252-3. https://doi.org/10.1056/NEJM197908023010506
  12. Hamnvik OP, Larsen PR, Marqusee E (2011). Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst, 103, 1572-87. https://doi.org/10.1093/jnci/djr373
  13. Heidemann PH, Stubbe P, Beck W (1981). Transient secondary hypothyroidism and thyroxine binding globulin deficiency in leukemic children during polychemotherapy: an effect of L-asparaginase. Eur J Pediatr, 136, 291-5. https://doi.org/10.1007/BF00442997
  14. Hellevik AI, Asvold BO, Bjoro T, et al (2009). Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol Biomarkers Prev, 18, 570-4. https://doi.org/10.1158/1055-9965.EPI-08-0911
  15. Hollowell JG, Staehling NW, Flanders WD, et al (2002). Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab, 87, 489-99. https://doi.org/10.1210/jcem.87.2.8182
  16. Huang J, Jin L, Ji G, et al (2013). Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine. BMC Cancer, 13, 334. https://doi.org/10.1186/1471-2407-13-334
  17. Khan NF, Mant D, Carpenter L, Forman D, Rose PW (2011). Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study. Br J Cancer, 105, 29-37. https://doi.org/10.1038/bjc.2011.420
  18. LeGrys VA, Funk MJ, Lorenz CE, et al (2013). Subclinical hypothyroidism and risk for incident myocardial infarction among postmenopausal women. J Clin Endocrinol Metab, 98, 2308-17. https://doi.org/10.1210/jc.2012-4065
  19. Mamby CC, Love RR, Lee KE (1995). Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer. J Clin Oncol, 13, 854-7. https://doi.org/10.1200/JCO.1995.13.4.854
  20. Massart C, Le Tellier C, Lucas C, et al (1992). Effects of cisplatin on human thyrocytes in monolayer or follicle culture. J Mol Endocrinol, 8, 243-8. https://doi.org/10.1677/jme.0.0080243
  21. Meistrich ML,Vassilopoulou-Sellin R, Lipshultz LI (1997). Adverse effects of treatment: gonadal dysfunction. In: DeVita VT, Hellman S, Rosenberg SA, editors. cancer, principles and practice of oncology, ed 5, New York: Lippincott-Raven Publishers, 2758-73.
  22. Stuart NS, Woodroffe CM, Grundy R, Cullen MH (1990). Longterm toxicity of chemotherapy for testicular cancer-the cost of cure. Br J Cancer, 61, 479-84. https://doi.org/10.1038/bjc.1990.106
  23. Surks MI, Sievert R (1995). Drugs and thyroid function. N Engl J Med, 333, 1688-94. https://doi.org/10.1056/NEJM199512213332507
  24. Sutcliffe SB, Chapman R, Wrigley PF (1981). Cyclical combination chemotherapy and thyroid function in patients with advanced Hodgkin's disease. Med Pediatr Oncol, 9, 439-48. https://doi.org/10.1002/mpo.2950090505
  25. Torino F, Barnabei A, Paragliola R, et al (2013). Thyroid dysfunction as an unintended side effect of anticancer drugs. Thyroid, 23, 1345-66. https://doi.org/10.1089/thy.2013.0241
  26. Tosovic A, Bondeson AG, Bondeson L, Ericsson UB, Manjer J (2013). Triiodothyronine levels in relation to mortality from breast cancer and all causes: a population-based prospective cohort study. Eur J Endocrinol, 168, 483-90. https://doi.org/10.1530/EJE-12-0564
  27. Tosovic A, Becker C, Bondeson AG, et al (2012). Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk. Int J Cancer, 131, 2126-33. https://doi.org/10.1002/ijc.27470
  28. Varughese AA, Poothiode U, Manjula VD (2015). Descriptive study on selected risk factors and histopathology of breast carcinoma in a tertiary care centre in kerala, indiawith special reference to women under 40 years old. Asian Pac J Cancer Prev, 16, 181-4. https://doi.org/10.7314/APJCP.2015.16.1.181
  29. Warner MH, Beckett GJ (2010). Mechanisms behind the nonthyroidal illness syndrome: an update. J Endocrinol, 205, 1-13. https://doi.org/10.1677/JOE-09-0412
  30. Yeung SCJ, Chiu AC, Vassilopoulou-Sellin R, Gagel RF (1998). The endocrine effects of nonhormonal antineoplastic therapy. Endocrine Rev, 19, 144-72. https://doi.org/10.1210/edrv.19.2.0328

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