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Published in: Breast Cancer Research and Treatment 2/2015

Open Access 01-01-2015 | Clinical trial

Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01)

Authors: S. de Groot, L. G. M. Janssen, A. Charehbili, E. M. Dijkgraaf, V. T. H. B. M. Smit, L. W. Kessels, A. van Bochove, H. W. M. van Laarhoven, E. Meershoek-Klein Kranenbarg, A. E. van Leeuwen-Stok, C. J. H. van de Velde, H. Putter, J. W. R. Nortier, J. J. M. van der Hoeven, H. Pijl, J. R. Kroep

Published in: Breast Cancer Research and Treatment | Issue 2/2015

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Abstract

This side study investigated the effect of chemotherapy on thyroid function and the extent to which it can predict pathological complete response (pCR) in patients with early breast cancer taking part in NEOZOTAC phase III trial, randomizing between neoadjuvant chemotherapy with or without additional zoledronic acid. Moreover, we examined the impact of thyroid function on toxicity. Serum samples of 38 patients were available for analyses. Free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were compared between baseline and before the 6th cycle and between subjects with and without pCR. The relation between toxicity and the variation in fT4 and TSH levels during chemotherapy was tested. Samples at baseline and before the 6th cycle were available for 31 and 21 patients, respectively. The mean baseline fT4 level was 16.0 pmol/L and TSH level 1.11 mU/L, and these did not differ between both arms at each time point. During six cycles of chemotherapy, fT4 levels decreased (p = 0.0001), and TSH levels increased significantly (p = 0.019). Interestingly, the decrease of fT4 was significantly greater in patients without nausea, vomiting, or neuropathy, than in patients with those side effects (p = 0.037, p = 0.043, and p = 0.050, respectively). Baseline TSH levels tended to be higher in patients with pCR (p = 0.035 univariate analysis and p = 0.074 multivariate analysis). Chemotherapy blunts thyroid function, which was associated with less side effects. These data urge further evaluation of the effects of thyroid function on toxicity and outcome of breast cancer therapy.
Literature
1.
go back to reference 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 168:483–490PubMedCrossRef 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 168:483–490PubMedCrossRef
2.
go back to reference 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 131:2126–2133PubMedCrossRef 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 131:2126–2133PubMedCrossRef
3.
go back to reference Hellevik AI, Asvold BO, Bjoro T, Romundstad PR, Nilsen TI, Vatten LJ (2009) Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol Biomarkers Prev 18:570–574PubMedCrossRef Hellevik AI, Asvold BO, Bjoro T, Romundstad PR, Nilsen TI, Vatten LJ (2009) Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol Biomarkers Prev 18:570–574PubMedCrossRef
4.
go back to reference Moeller LC, Fuhrer D (2013) Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer 20:R19–R29PubMedCrossRef Moeller LC, Fuhrer D (2013) Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer 20:R19–R29PubMedCrossRef
5.
go back to reference Cristofanilli M, Yamamura Y, Kau SW et al (2005) Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer 103:1122–1128PubMedCrossRef Cristofanilli M, Yamamura Y, Kau SW et al (2005) Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer 103:1122–1128PubMedCrossRef
6.
go back to reference Hercbergs AA, Goyal LK, Suh JH et al (2003) Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study. Anticancer Res 23:617–626PubMed Hercbergs AA, Goyal LK, Suh JH et al (2003) Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study. Anticancer Res 23:617–626PubMed
7.
go back to reference Eke KC, Turkmen YS, Temizel M et al (2013) Serum resistin and insulin-like growth factor-1 levels in patients with hypothyroidism and hyperthyroidism. J Thyr Res 2013:306750 Eke KC, Turkmen YS, Temizel M et al (2013) Serum resistin and insulin-like growth factor-1 levels in patients with hypothyroidism and hyperthyroidism. J Thyr Res 2013:306750
8.
go back to reference Dinda S, Sanchez A, Moudgil V (2002) Estrogen-like effects of thyroid hormone on the regulation of tumor suppressor proteins, p53 and retinoblastoma, in breast cancer cells. Oncogene 21:761–768PubMedCrossRef Dinda S, Sanchez A, Moudgil V (2002) Estrogen-like effects of thyroid hormone on the regulation of tumor suppressor proteins, p53 and retinoblastoma, in breast cancer cells. Oncogene 21:761–768PubMedCrossRef
9.
go back to reference Figueiredo NB, Cestari SH, Conde SJ et al (2014) Estrogen-responsive genes overlap with triiodothyronine-responsive genes in a breast carcinoma cell line. ScientificWorldJournal 2014:969404PubMedCentralPubMed Figueiredo NB, Cestari SH, Conde SJ et al (2014) Estrogen-responsive genes overlap with triiodothyronine-responsive genes in a breast carcinoma cell line. ScientificWorldJournal 2014:969404PubMedCentralPubMed
10.
go back to reference Hall LC, Salazar EP, Kane SR, Liu N (2008) Effects of thyroid hormones on human breast cancer cell proliferation. J Steroid Biochem Mol Biol 109:57–66PubMedCrossRef Hall LC, Salazar EP, Kane SR, Liu N (2008) Effects of thyroid hormones on human breast cancer cell proliferation. J Steroid Biochem Mol Biol 109:57–66PubMedCrossRef
11.
go back to reference Vonderhaar BK, Greco AE (1982) Effect of thyroid status on development of spontaneous mammary tumors in primiparous C3H mice. Cancer Res 42:4553–4561PubMed Vonderhaar BK, Greco AE (1982) Effect of thyroid status on development of spontaneous mammary tumors in primiparous C3H mice. Cancer Res 42:4553–4561PubMed
12.
go back to reference Pinto M, Soares P, Ribatti D (2011) Thyroid hormone as a regulator of tumor induced angiogenesis. Cancer Lett 301:119–126PubMedCrossRef Pinto M, Soares P, Ribatti D (2011) Thyroid hormone as a regulator of tumor induced angiogenesis. Cancer Lett 301:119–126PubMedCrossRef
13.
go back to reference Nelson M, Hercbergs A, Rybicki L, Strome M (2006) Association between development of hypothyroidism and improved survival in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 132:1041–1046PubMedCrossRef Nelson M, Hercbergs A, Rybicki L, Strome M (2006) Association between development of hypothyroidism and improved survival in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 132:1041–1046PubMedCrossRef
14.
go back to reference Ditsch N, Liebhardt S, Von KF et al (2010) Thyroid function in breast cancer patients. Anticancer Res 30:1713–1717PubMed Ditsch N, Liebhardt S, Von KF et al (2010) Thyroid function in breast cancer patients. Anticancer Res 30:1713–1717PubMed
15.
go back to reference Cutuli B, Quentin P, Rodier JF, Barakat P, Grob JC (2000) Severe hypothyroidism after chemotherapy and locoregional irradiation for breast cancer. Radiother Oncol 57:103–105PubMedCrossRef Cutuli B, Quentin P, Rodier JF, Barakat P, Grob JC (2000) Severe hypothyroidism after chemotherapy and locoregional irradiation for breast cancer. Radiother Oncol 57:103–105PubMedCrossRef
16.
go back to reference Bruning P, Bonfrer J, De Jong-Bakker M, Nooyen W, Burgers M (1985) Primary hypothyroidism in breast cancer patients with irradiated supraclavicular lymph nodes. Br J Cancer 51:659–663PubMedCentralPubMedCrossRef Bruning P, Bonfrer J, De Jong-Bakker M, Nooyen W, Burgers M (1985) Primary hypothyroidism in breast cancer patients with irradiated supraclavicular lymph nodes. Br J Cancer 51:659–663PubMedCentralPubMedCrossRef
17.
go back to reference Joensuu H, Viikari J (1986) Thyroid function after postoperative radiation therapy in patients with breast cancer. Acta Radiol Oncol 25:167–170PubMedCrossRef Joensuu H, Viikari J (1986) Thyroid function after postoperative radiation therapy in patients with breast cancer. Acta Radiol Oncol 25:167–170PubMedCrossRef
18.
go back to reference Kailajarvi M, Ahokoski O, Virtanen A, Salminen E, Irjala K (2000) Alterations in laboratory test results during adjuvant breast cancer treatment. Clin Chem Lab Med 38:443–451PubMedCrossRef Kailajarvi M, Ahokoski O, Virtanen A, Salminen E, Irjala K (2000) Alterations in laboratory test results during adjuvant breast cancer treatment. Clin Chem Lab Med 38:443–451PubMedCrossRef
19.
go back to reference 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 13:334PubMedCentralPubMedCrossRef 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 13:334PubMedCentralPubMedCrossRef
20.
go back to reference Charehbili AV, van de Ven S, van d Smit VT et al (2014) Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01). Ann Oncol 25:998–1004PubMedCrossRef Charehbili AV, van de Ven S, van d Smit VT et al (2014) Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01). Ann Oncol 25:998–1004PubMedCrossRef
21.
go back to reference Ogston KN, Miller ID, Payne S et al (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12:320–327PubMedCrossRef Ogston KN, Miller ID, Payne S et al (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12:320–327PubMedCrossRef
22.
go back to reference Von MG, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804CrossRef Von MG, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804CrossRef
23.
go back to reference Kuerer HM, Newman LA, Smith TL et al (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469PubMed Kuerer HM, Newman LA, Smith TL et al (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469PubMed
24.
go back to reference 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(Suppl 1):S29–S37PubMedCentralPubMedCrossRef 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(Suppl 1):S29–S37PubMedCentralPubMedCrossRef
25.
go back to reference Warner MH, Beckett GJ (2010) Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol 205:1–13PubMedCrossRef Warner MH, Beckett GJ (2010) Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol 205:1–13PubMedCrossRef
26.
go back to reference Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG (2004) Thyroid status, disability and cognitive function, and survival in old age. JAMA 292:2591–2599PubMedCrossRef Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG (2004) Thyroid status, disability and cognitive function, and survival in old age. JAMA 292:2591–2599PubMedCrossRef
28.
go back to reference Funakoshi T, Shimada YJ (2013) Risk of hypothyroidism in patients with cancer treated with sunitinib: a systematic review and meta-analysis. Acta Oncol 52:691–702PubMedCrossRef Funakoshi T, Shimada YJ (2013) Risk of hypothyroidism in patients with cancer treated with sunitinib: a systematic review and meta-analysis. Acta Oncol 52:691–702PubMedCrossRef
29.
go back to reference Sabatier R, Eymard JC, Walz J et al (2012) Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma? Ann Oncol 23:714–721PubMedCrossRef Sabatier R, Eymard JC, Walz J et al (2012) Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma? Ann Oncol 23:714–721PubMedCrossRef
30.
go back to reference Riesenbeck LM, Bierer S, Hoffmeister I et al (2011) Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib. World J Urol 29:807–813PubMedCrossRef Riesenbeck LM, Bierer S, Hoffmeister I et al (2011) Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib. World J Urol 29:807–813PubMedCrossRef
Metadata
Title
Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01)
Authors
S. de Groot
L. G. M. Janssen
A. Charehbili
E. M. Dijkgraaf
V. T. H. B. M. Smit
L. W. Kessels
A. van Bochove
H. W. M. van Laarhoven
E. Meershoek-Klein Kranenbarg
A. E. van Leeuwen-Stok
C. J. H. van de Velde
H. Putter
J. W. R. Nortier
J. J. M. van der Hoeven
H. Pijl
J. R. Kroep
Publication date
01-01-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-3256-4

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