Abstract P3-06-50: Thyroid function is associated with the response to neoadjuvant chemotherapy in breast cancer patients: Results from the NEOZOTAC trial on behalf of the Dutch Breast Cancer Research Group (BOOG 2010-01)
Authors: de Groot S , Charehbili A , Janssen L GM , Dijkgraaf E M , Smit V THBM , Kessels L W , van Bochove A , van Laarhoven H WM , Meershoek-Klein Kranenbarg E , van Leeuwen-Stok A E , Liefers G J , van de Velde C JH , Nortier J WR , van der Hoeven J JM , Pijl H , Kroep J R 
Published: May 2015

Abstract
Background: Thyroid hormones, regulators of metabolism and development in healthy tissue, stimulate tumor growth in vitro and are associated with breast cancer risk. We investigated the effect of chemotherapy on thyroid function and the extent to which it can predict the pathological response in patients with HER2 negative stage II/III breast cancer taking part in the NEOZOTAC phase III trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy with or without additional zoledronic acid. Moreover, we examined the impact of thyroid function on chemotherapy toxicity.
Methods: Serum samples of 38 of the 105 patients who participated in the side study of the NEOZOTAC trial were available for analyses. Serum free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were measured at baseline and compared with fT4 and TSH levels before the 2nd and 6th chemotherapy cycle. FT4 and TSH levels were also compared between subjects with and without pathological complete response (pCR). The relation between toxicity, per side effect of any CTC grade, and the variation in fT4 and TSH levels during chemotherapy was tested.
Results: Serum samples at baseline, before the 2nd chemotherapy cycle and at end of treatment were available for 31, 30 and 21 patients, respectively. In the total population, the mean baseline fT4 level was 16,0pmol/L and the mean TSH level 1,11mU/L. There were no differences between subjects solely treated with TAC chemotherapy and subjects treated with zoledronic acid as an adjunct to TAC with respect to the mean fT4 and TSH at each time point. Baseline TSH levels tended to be higher in patients who achieved pCR (p=0.035 univariate analysis and p=0.074 multivariate analysis) (Table 1). During 6 cycles of chemotherapy, fT4 levels decreased (p&lt;0.000) and TSH levels increased significantly (p=0.019). Interestingly, the decrease of fT4 was significantly greater in patients without nausea, vomiting or sensory neuropathy, than in patients with those side effects (p=0.037, p=0.043 and p=0.050 respectively).
CharacteristicUnivariate analysisMultivariate analysis OR95%CIP valueOR95%CIP valueN stage: N0 vs. N+0.330.03-3.640.368T stage: &lt;5cm vs. &gt;5cm0.330.03-3.630.333ER receptor: Pos vs. Neg2.560.20-33.10.473fT40.780.43-1.420.4170.660.33-1.290.581TSH3.241.09-9.700.03517.30.76-3910.074Table 1. Univariate and multivariate logistic regression models of baseline characteristics and TSH and fT4 predictive of pCR.
Conclusion: TSH levels at baseline were higher in breast cancer patients with pCR. Chemotherapy blunts thyroid function, and a large decline of fT4 was associated with less side effects. These data suggest that thyroid hormones may interact with chemotherapy to modulate treatment (side-) effects in patients with breast cancer.
Citation Format: S de Groot, A Charehbili, L GM Janssen, E M Dijkgraaf, V THBM Smit, L W Kessels, A van Bochove, H WM van Laarhoven, E Meershoek-Klein Kranenbarg, A E van Leeuwen-Stok, G J Liefers, C JH van de Velde, J WR Nortier, J JM van der Hoeven, H Pijl, J R Kroep. Thyroid function is associated with the response to neoadjuvant chemotherapy in breast cancer patients: Results from the NEOZOTAC trial on behalf of the Dutch Breast Cancer Research Group (BOOG 2010-01) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-50.