Evaluation of thyroid dysfunction in breast cancer before surgery.
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1 Biomeical Research 2017; 28 (20): ISSN X Evaluation of thyroi ysfunction in breast cancer before surgery. Mohamma Reza Motie *, Reza Taheri, Faegheh Noorian Surgical Oncology Research Center, Mashha University of Meical Sciences, Mashha, Iran Abstract Introuction: Breast cancer is the most common malignancy in women an is one of the leaing causes of eath in women. Hence, the stuy of factors involve in the incience an progression of isease is of great importance. In this stuy, the relationship between breast cancer an thyroi isorers will be iscusse. Methos: In a case-control stuy, 86 women with confirme breast cancer an 50 age-matche healthy women as controls were stuie for 12 months in the Cancer Research Center, Imam Reza hospital, Mashha University of Meical Sciences, Iran. After examination of the thyroi, serum level of Thyrotropin (TSH), Thyroxine (T4), Triioothyronine (T3) an Anti-Thyroi Peroxiase Antiboy (anti-tpo AB) were teste by raioimmunoassay. The results were compare between the two groups an ifferent pathological subtypes of breast cancer. Results: Mean serum TSH level was not significantly ifferent between the two groups, but the mean serum levels of T4 an anti-tpo AB was higher in patients (p<0.05). levels of TSH an T4 were observe in 5.8% an 2.3% of the patient an 12% an 8% of the control group, respectively. Also, ecrease TSH an T4 levels were observe in 7% an 2.3% of the patient an 5% an 0% of the control group, respectively. As well, increase levels of T3 an anti-tpo AB were observe in 0% an 20.9% of patients an in 4% an 8% of the control group, respectively. Conclusion: Although there was a significant ifference between the groups regaring the anti-tpo AB level, but no obvious connection between thyroi function an breast cancer was foun in this stuy. Therefore, stuies with larger sample sizes are require to achieve more qualifie results. Keywors: Breast cancer, Thyroi isorer, Thyroi hormones. Accepte on July 17, 2017 Introuction Breast cancer is the most common cancer in women an the secon leaing cause of eath from cancer [1]. It is shown that breast cancer is more common in societies with high prevalence of goitre isease an hypothyroiism than those with euthyroi or hyperthyroi [2,3]. Breast cancer is a hormone-epenent tumor. In aition, stuies suggest that thyroi isease is more prevalent in women with breast cancer [4,5]. Finings show that almost all types of thyroi isorers, incluing noular hyperplasia, hyperthyroiism an thyroi cancer may be connecte to breast cancer [6]. Although the relationship between breast cancer an thyroi isorers is a controversial issue, finings show that the incience of breast cancer is higher in patients with thyroi isorers [2,6]. Stuies also show that the risk of breast cancer increases after thyroiectomy [7]. Eviences suggest that hypothyroiism may have a protective role against breast cancer [8]. As well, it is shown that the eficiency of circulating thyroi hormone may cause the excessive prouction of prolactin an estrogen in the epithelium of mammary glans leaing to breast cancer [9]. Hyperthyroiism is also associate with a reuce risk of breast cancer. Therefore, in patients with hyperthyroiism an non-operable breast cancer, the growth of tumors is rather slow [9]. Stuies have also shown that hyperthyroiism is associate with the evelopment of breast cancer in premenopausal women [10]. Currently, the role of thyroi hormones in the pathobiology of breast cancer is unknown [11]. If such association is confirme, evaluation of the thyroi function can be use for screening the risk of breast cancer. Since little researches have been conucte on the relationship between thyroi isease an breast cancer in Iranian patients, therefore, in this stuy thyroi function an serum levels of the thyrotropin (TSH), thyroxine (T4), triioothyronine (T3) an anti-thyroi peroxiase antiboy (anti-tpo AB) were evaluate in patients with breast cancer prior to surgery to etermine the possible association between thyroi isease an the incience an progression of breast cancer. Biome Res 2017 Volume 28 Issue
2 Motie/Taheri/Noorian Material an Methos Sample collection This case-control stuy was conucte from January 2013 to 2014 in the Cancer Research Center at Imam Reza hospital, Mashha, Iran on patients with breast cancer who unerwent simple or moifie an conservative mastectomy an other patients without breast cancer as control groups. Patients in the control group ha not been iagnose with breast cancer, but ha unergone surgery. Accoring to the results of previous stuies in which the prevalence anti-tpo AB in women with breast cancer was 34% in comparison with 36% in control group, an also given that the allocation ratio is equal to 0.55, an consiering the significance level of 5% an the power of at least 80% for this test, the minimum sample size for the control an experimental group was efine 50 an 86 participants, respectively. Before enrolment, informe consent was obtaine from participants an the stuy was confirme by the Ethical Committee. Clinical evaluation After primary meical examination an a ay before surgery, serum level of TSH, T4, T3 an anti-tpo AB were assesse in both groups by raioimmunoassay. The normal range consiere for thyroi hormones were 0.5 to 4.5 mg/ml for TSH, 80 to 200 pg/ml for T3 an 4 to 12 ng/ml for T4. Also, the amount of anti-tpo AB more than 40 units/ml was consiere as positive. Thyroi function test The mean values for T3, T4, TSH an anti-tpo AB are shown in Table 1. Results showe that the ifference between the amount of TSH in the patient an control groups was not statistically significant (p=0.166). While a significant ifference in the mean T4 (p=0.001), T3 (p<0.001) an anti- Tpo AB (p=0.011) was observe between the two groups. Chisquare test or Fisher s exact test was use in contingency tables for a comparison between the two groups regaring the number of ecrease, increase an normal variables, an the results showe that the ifference between the two groups concerning T3 (p=0.028) an anti-tpo AB (p=0.048) was significant. However, the ifference in the amount of TSH (p=0.337) an T4 (p=0.173) within normal or abnormal range was not significant. Table 1. Demographic ata of stuy population. Breast group cancer Control group N=86 N=50 P value Age (y) 46.6 ± ± TSH (Mlu/ml) 2.59 ± ± T4 (ng/ml) 7.39 ± 2/ ± T3 (Pg/ml) ± ± <0.001 Anti-Tpo AB (Iu/m) ± ± Statistical analysis After ata collection an initial processing, the ata were analyze by SPSS v.19 statistical software. Initially the Kolmogorov-Smirnov test was use to evaluate the normality of the ata, an then the Stuent t-test for two inepenent groups (in the case of normal ata) an the nonparametric equivalent of Stuent t-tests such as the Mann-Whitney was use for ata analysis. For comparing the chi-square test an Fisher s exact test group also was use in contingency tables. The chi-square test an Fisher's exact test were also use in contingency tables for comparison of the rate in the groups. The significant level was consiere as p<0.05. TSH T4 T3 5 (5.8%) 6 (12%) (7%) 5 (10%) Normal 75 (87.2%) 39 (78%) 2 (2.3%) 4 (8%) (2.3%) 0 (0%) Normal 82 (95.3%) 46 (92%) 0 (0%) 2 (4%) Results 10 (11.6%) 1 (2%) Demographic ata Stuie participants inclue 86 patients with verifie breast cancer an other 50 patients without breast cancer as experimental an control group, respectively. The average age of stuy participants was 46.5 ± y. The age range of participants varie from y in patients group mean 46.6 ± y an y in mean 46.5 ± y in the control group, but the ifference in the two groups was not significant (p=0.957). Normal 76 (88.6%) 47 (94%) Anti-Tpo AB Positive 18 (20.9%) 4 (8%) Negative 68 (79.1%) 46 (92%) Histopathological examination Histopathological analysis showe that of 86 patients with breast cancer, 62 patients (72.1%) are with invasive uctal carcinoma, 23 (26.7%) with uctal carcinoma in situ an one (1.2%) with lobular carcinoma, an any of these patients were not positive for estrogen or progesterone receptor. The age 8626 Biome Res 2017 Volume 28 Issue 20
3 Evaluation of thyroi ysfunction in breast cancer before surgery range of patients in in-situ invasive carcinoma an uctal carcinoma in situ was y (mean ± y) an y (mean ± y), respectively, which showe no significant ifference between the average ages in the groups (p=0.525). As shown in Table 2, the average amount of TSH, T4, T3 an anti-tpo AB in the two groups of invasive uctal carcinoma an uctal carcinoma in situ were not significantly ifferent (p>0.05). The results of the ata survey regaring the percentage of ecrease, increase an normal variables in each group are shown in Table 2. As shown, the ifference between the two groups were not significant for any of the variables (p=0.884, p=0.302, p=0.824 an p=0.500 for TSH, T4, T3 an anti-tpo AB, respectively) (Table 3). Table 2. Comparison of the variables in patients with breast cancer base on histopathological iagnosis. Invasive uctal carcinoma Ductal carcinoma in situ P (N=62) (N=23) Age ± ± TSH (Mlu/ml) 2.65 ± ± T4 (ng/ml) 9.53 ± ± T3 (pg/ml) ± ± Anti-Tpo AB (Iu/ml) ± ± TSH 4 (6.5 %) 1 (4.3%) (6.5 %) 2 (8.7 %) Normal 54 (87.1 %) 20 (87 %) T4 4 (6.5 %) 0 (0 %) (3.2 %) 0 (0%) Normal 56 (90.3 %) 23 (100 %) T3 0 (0%) 0 (0%) (11.3 %) 3 (13 %) Normal 55 (88.7 %) 20 (87 %) Anti-Tpo AB Positive 12 (19.4 %) 6 (26.1 %) 0.5 Negative 50 (80.6 %) 17 (73.9 %) The number of involve lymph noes 3.29 ± ± The comparison of the two groups regaring the number of involve lymph noes showe that the mean number of lymph noes involve in invasive uctal carcinoma an uctal carcinoma in situ groups were 3.29 an 1.65, respectively, inicating the significance of the ifference between the two groups (p=0.018). Table 3. Associations between thyroi tests in two groups of case an control. O ratio Thyroi ysfunction T3 ysfunction T4 ysfunction TSH ysfunction % confience interval Anti TPO ysfunction Discussion The results of some stuies have shown that thyroi isease is more common among women with breast cancer. In some stuies, the relationship between various types of thyroi isease, incluing noular hyperplasia, hyperthyroiism an thyroi carcinoma with breast cancer have been ientifie [6,12]. Also, various stuies have shown that the incience of Autoimmune Thyroi Disorers (AITD) is more common among patients with breast cancer [13,14]. Several stuies on the relationship between serum levels of anti-tpo AB, thyroi volume, amount of FT3, FT4, TSH, an estraiol with breast cancer have shown that anti-tpo AB is significantly higher in women with breast cancer, an these results emonstrate a possible association between breast cancer an autoimmune thyroi isorers [13,15-18]. In aition, along with the increasing prevalence of anti-tpo AB in women with breast Biome Res 2017 Volume 28 Issue
4 Motie/Taheri/Noorian cancer, it was foun that a significant correlation may exist between breast cancer an autoimmune an non-autoimmune thyroi isease [6,19]. In consistent with some stuies, in the present stuy, the average amount of anti-tpo AB (p=0.011) an T4 (p=0.001) were significantly higher in patients with breast cancer than those in the control group [16,20]. Moreover, in our stuy, the average amount of T3 (p=0.001) an TSH (p=0.166) in patients with breast cancer were significantly lower than those in the control group, an these results were consistent with the results of similar stuies in this area [21-24]. Laboratory finings have shown that thyroi hormones can have estrogen-like effect on breast cancer. As well, it has been shown that receptors of thyroi hormones may have an effect on the proliferation an ifferentiation of breast cancer cells [25]. Fierabracci et al. reporte a strong relationship between thyroi autoimmune isorer an breast cancer [13]. The ratio of Free T3/Free T4 is also introuce as an inicator of breast carcinoma, so that this ratio may increase in patients with breast cancer [18]. As well, the finings show that any alterations in the level of T4 may be associate with increase risk of breast cancer. While, patients with high anti-tpo AB are at lower risk of breast cancer. As well, serum level of T3, total T4 an free T4 were higher in patients with breast carcinoma [20,26,27]. Stuies have also shown that thyroi iseases are associate with tumor grae in women with breast cancer, an the thyroi isorers increase with increasing the tumor grae [28]. But, several stuies coul not fin any significant association between enlargement of the thyroi glan or other thyroi isorers with breast cancer [19,22]. Several reasons such as ifferences in the stuie sample size, evaluation methos of thyroi iseases as well as the accuracy an sensitivity of laboratory methos may cause ifferences in the results of various stuies. Another important factor is the racial ifferences an their impact on the incience of thyroi iseases. The results of this stuy o not approve the relationship between thyroi isease an breast cancer, but to reach conclusive finings in this regar, further research is recommene in similar centers. Conclusion Although there was a significant ifference between the groups regaring the anti-tpo AB, T3 an T4 level, but the results of this stuy o not support correlation between thyroi function an the incience or exacerbation of breast cancer. Therefore, to achieve more qualifie results further stuies with larger sample sizes an appropriate stuy esign are require. Acknowlegment The results escribe in this paper constitute as a part of a MD thesis submitte by the secon author to Mashha University of Meical Sciences. The stuy was supporte by the vice chancellor for research at Mashha University of Meical Sciences. References 1. Jemal A, Bray F, Center MM, Ferlay J, War E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: Shering SG, Zbar AP, Moriarty M, McDermott EW, O'Higgins NJ, Smyth PP. Thyroi isorers an breast cancer. Eur J Cancer Prev 1996; 5: Giani C, Fierabracci P, Bonacci R, Gigliotti A, Campani D, De Negri F. Relationship between breast cancer an thyroi isease: relevance of autoimmune thyroi isorers in breast malignancy. J Clin Enocrinol Metab 1996; 81: Clarke R, Dickson RB, Brunner N. The process of malignant progression in human breast cancer. Ann Oncol 1990; 1: Gogas J, Kouskos E, Tseleni-Balafouta S, Markopoulos C, Revenas K, Gogas G. Autoimmune thyroi isease in women with breast carcinoma. Eur J Surg Oncol 2001; 27: Turken O, NarIn Y, DemIrbas S, One ME, Sayan O, KanemIr EG. Breast cancer in association with thyroi isorers. Breast Cancer Res 2003; 5: Perry M, Golie DJ, Self M. Thyroi function in patients with breast cancer. Ann R Coll Surg Engl 1978; 60: Smyth PP. The thyroi, ioine an breast cancer. Breast Cancer Res 2003; 5: Vorherr H. Thyroi isease in relation to breast cancer. Klin Wochenschr 1978; 56: Saraiva P, Figueireo N, Paovani C, Brentani M, Nogueira C. Profile of thyroi hormones in breast cancer patients. Braz J Me Biol Res 2005; 38: Smyth P. Thyroi isease an breast cancer. J Enocrinol Invest 1993; 16: Agarwal DP, Soni TP, Sharma OP, Sharma S. Synchronous malignancies of breast an thyroi glan: a case report an review of literature. J Cancer Res Ther 2007; 3: Fierabracci P, Pinchera A, Campani D, Pollina LE, Giustarini E, Giani C. Association between breast cancer an autoimmune thyroi isorers: no increase of lymphocytic infiltrates in breast malignant tissues. J Enocrinol Invest 2006; 29: Giustarini E, Pinchera A, Fierabracci P, Roncella M, Fustaino L, Mammoli C. Thyroi autoimmunity in patients with malignant an benign breast iseases before surgery. Eur J Enocrinol 2006; 154: Sabitha, Suneetha, Mohanty S, Rao P. Serum anti-tpo levels in benign an malignant breast tumors. Inian J Clin Biochem 2009; 24: Ali A, Mir MR, Bashir S, Hassan T, Bhat SA. Relationship between the levels of serum thyroi hormones an the risk of breast cancer. J Biol Agric Health 2011; 1: Smyth PP, Shering SG, Kilbane MT, Murray MJ, McDermott EW, Smith DF. Serum thyroi peroxiase autoantiboies, thyroi volume, an outcome in breast carcinoma. J Clin Enocrinol Metab 1998; 83: Biome Res 2017 Volume 28 Issue 20
5 Evaluation of thyroi ysfunction in breast cancer before surgery 18. Ditsch N, Liebhart S, Von Koch F, Lenhar M, Vogeser M, Spitzweg C. Thyroi function in breast cancer patients. Anticancer Res 2010; 30: Michalaki V, Koni-Pafiti A, Gennatas S, Antoniou A, Primetis H, Gennatas C. Breast cancer in association with thyroi isorers. J Buon 2009; 14: Wang G, Chen X-S, Mao Y, Li Y-F, Chen W-G, Shen K-W. Patients with breast cancer have a higher level of serum free thyroxine (T4) compare with those with benign breast iseases. Tumor 2014; 34: Takatani O, Okumoto T, Kosano H, Nishia M, Hiraie H, Tamakuma S. Relationship between the levels of serum thyroi hormones or estrogen status an the risk of breast cancer genesis in Japanese women. Cancer Res 1989; 49: Kuijpens JL, Nyklictek I, Louwman MW, Weetman TA, Pop VJ, Coebergh JW. Hypothyroiism might be relate to breast cancer in post-menopausal women. Thyroi 2005; 15: Saraiva P, Figueireo N, Paovani C, Brentani M, Nogueira C. Profile of thyroi hormones in breast cancer patients. Brazil Me Biol Res 2005; 38: Rose DP, Davis TE. Plasma triioothyronine concentrations in breast cancer. Cancer 1979; 43: Tosovic A, Boneson AG, Boneson L, Ericsson UB, Malm J, Manjer J. Prospectively measure triioothyronine levels are positively associate with breast cancer risk in postmenopausal women. Breast Cancer Res 2010; 12: Cengiz O, Bozkurt B, Unal B, Yilirim O, Karabeyoglu M, Eroglu A. The relationship between prognostic factors of breast cancer an thyroi isorers in Turkish women. J Surg Oncol 2004; 87: Tosovic A, Becker C, Boneson AG, Boneson L, Ericsson UB, Malm J. Prospectively measure thyroi hormones an thyroi peroxiase antiboies in relation to breast cancer risk. Int J Cancer 2012; 131: Lemaire M, Baugnet-Mahieu L. Thyroi function in women with breast cancer. Eur J Cancer Clin Oncol 1986; 22: * Corresponence to Mohamma Reza Motie Surgical Oncology Research Center Mashha University of Meical Sciences Mashha Iran Biome Res 2017 Volume 28 Issue
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