Keywords: Breast cancer, goiter, thyroid, anti thyroid peroxidase (anti TPO) antibodies.

Transcription

1 Clinical Biochemistry Original Article International Journal of Chemical And Pharmaceutical Research ISSN Volume 2, Issue 7, July Glorigin Lifesciences Private Limited. EVALUATION OF SERUM ANTI THYROID PEROXIDASE ANTIBODIES IN CARCINOMA BREAST OF INDIAN WOMEN Venkata Bharat Kumar Pinnelli 1, Wilma Delphine Silvia CR 2, Suresh KP 3 Abstract Conflicting results have indicated a relationship between breast cancer and thyroid autoantibodies. Hence this study was aimed to evaluate thyroid function by estimating thyroxine (T 4 ), thyroid stimulating hormone (TSH) and serum anti thyroid peroxidase (anti TPO) antibodies level in women with breast cancer, women with benign breast tumor and healthy controls. This cross sectional study comprised of 20 women with malignant breast carcinoma and 20 women with benign breast carcinoma as cases and 30 healthy women were included as controls. Analyzed the serum for thyroxine, anti thyroid peroxidase (anti TPO) antibodies. Results of the study have shown significant elevation in serum levels of T 4, TSH, anti thyroid peroxidase antibodies in malignant breast cancer cases compared to benign carcinoma of breast and healthy controls. The statistically significant raised serum anti thyroid peroxidase antibodies with thyroid disorders in breast cancer patients shows an association between these two organs. Author Affiliations: 1 Department of Biochemistry, Vydehi Institute of Medical Sciences & Research Center, Bangalore, 2 Department of Biochemistry, Sapthagiri Institute of Medical Sciences & Research Center, Bangalore, 3 Project Directorate on Animal Disease Monitoring and Surveillance, Hebbal, Bangalore Keywords: Breast cancer, goiter, thyroid, anti thyroid peroxidase (anti TPO) antibodies. * Corresponding Author: Dr. Wilma Delphine Silvia CR. MD., DNB, Professor & HOD, Department of Biochemistry, Sapthagiri Institute of Medical Sciences and Research Centre, #15, Chikkasandra, Hesaraghatta Main Road, Bangalore , Karnataka, India. Contact Number: , Fax number: , ID: widel2008@gmail.com,widel@rediffmail.com. Intl. J Chem Pharm Res 2013;2(7):

2 1. INTRODUCTION Breast cancer is the most common cancer of women, and its incidence is rising especially a rise of 26% in breast cancer i.e., about 1.7 million women will be affected by breast cancer in 2020, [1, mostly in developing countries 2]. The progression of many human cancers including breast are known to be influenced by steroid hormones [3, 4]. The estrogen hormone levels play an important role in growth and development of breast cancer [5]. The environmental factors, pathological conditions and physiological agents and hormone levels of thyroid gland influence the development of breast cancer [6]. Deaminated form of tetraiodothyroacetic acid (tetrac), which antagonizes the proliferative action of thyroid hormones, was found to possess anti-cancer functions through its ability to inhibit cellular proliferation and angiogenesis [7]. Thyroid hormone and oestrogen share similar pathways in regulating growth and proliferation of the cells in the target tissues, including cancer cells. The evaluation of presence of the receptors of these hormones is important in understanding the progression of the cancer [8]. One of the recent study states that a change in the expression of the thyroid hormone receptors in breast cancer tissues, which says that these receptors are deregulated which inturn increases the risk for development of breast cancer [9, 10]. Therefore, in this case control study, only patients with newly diagnosed breast cancer or benign breast disease were included before surgery, chemotherapy, radiation or antihormonal therapy with or without coincident thyroid enlargement and healthy controls investigated for thyroxine, TSH and anti TPO antibodies. 2. MATERIAL AND METHODS This cross sectional study included the patients visiting department of Surgical Oncology. 40 cases of women with breast cancer within the age group of years were included in the study. Fine needle aspiration cytology (FNAC) was carried out in these cases; hence the diagnosis was confirmed histopathologically. Based on the histopathological findings, out of 40 cases 20 were ductal cell carcinoma (malignant) and 20 were fibroadenoma (benign) cases. Family history was collected. Most patients belonged to low socio-economic status group. Patients who had undergone therapy for thyroid disease were excluded from the study. Only those patients whose breast carcinoma was first diagnosed during the period of the study were included. Women who were pregnant, women with chronic diseases/ diabetes mellitus/renal disorders/on hormone replacement therapy were excluded from this study. None of the patients had diabetes mellitus, tuberculosis, generalized infections, liver or kidney disease. None of them were smokers or alcohol abusers. Anti TPO antibody levels of 30 age matched healthy female subjects, who visited the hospital for general health check up were considered as controls. Institutional ethics committee clearance was obtained and Intl. J Chem Pharm Res 2013;2(7):

3 informed consent was signed by all the subjects participated in this study. Blood levels of thyroid profile and anti TPO antibody analysis were carried out with Beckman Coulter Access 2 instrument using the was done to check whether all the samples had equal variance. A significant difference in variance was found with P< ANOVA showed statistically significant difference in the average anti TPO antibodies among the three principle of electro chemiluminescence groups (P< 0.001). Tukey s HSD test was done (Beckman Coulter, Inc. USA) Statistical analysis: Statistical software namely SPSS 15.0 was used. ANOVA and Tukey s HSD test carried out to findout the siginificant difference. P value <0.05 was considered to be significant. 3. RESULTS Mean values of anti TPO antibodies in for pair wise comparison of the average anti TPO antibodies. Table 1 shows the mean values of anti TPO antibodies levels. The study showed a statistically significant difference in anti TPO antibodies between malignant and benign groups (P<0.001). Statistically significant difference in anti TPO antibodies between malignant and control groups (P< 0.001). The study did not ductal cell carcinoma cases (malignant), show any significant difference in anti TPO Fibroadenoma (benign) & healthy controls were antibodies between benign & control groups (P 96.3±76.18, 20.01±16.88 & 15.47±5.63 >0.05). (Table 1) respectively. A test for homogeneity of variances Table 1: Age, Thyroid Profile and Anti-TPO levels in cases and controls Parameters Ductal cell carcinoma Fibroadenoma (n=20) Control (n=30) (n=20) (Benign) (mean ± SD) (Malignant) (mean ± SD) (mean ± SD) Age (years) 54.2 ± ± ±10.8 T3 (ng/ml) 0.92± ± ±0.61 T4 (µg/dl) 6.45± ± ±3.04 TSH (µiu/ml) 5.92± ± ±3.71 Serum anti TPO (IU/mL) 96.3± ± ± DISCUSSION Breast cancer is the most frequent malignant tumour in women worldwide with about 1 million women being affected [11]. The relationship between breast cancer and thyroid disease is a matter of controversy. Although associations with hyperthyroidism, hypothyroidism, thyroiditis and nontoxic goiter have been reported in the literature, no convincing evidence exists of a causal role for overt thyroid disease in breast cancer. The possible interactions between thyroid gland and Intl. J Chem Pharm Res 2013;2(7):

4 breast tissue are based on the common property of the mammary and thyroid epithelial cell to concentrate iodine by a membrane active transport mechanism as well as on the presence of TSH receptors in fatty tissue, which is abundant in mammary gland [12,13]. The studies on breast cancer patients indicates, an increased thyroid disorders in breast cancer patients, most commonly Hashimotos thyroiditis accounts to an increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer [12]. Alterations to expression of thyroid hormone receptors are found in breast cancer by several studies [6]. It suggests a role of thyroid hormone receptor in the progression of breast cancer. It was reported that most thyroid neoplastic and normal tissues were positive for mrna of both P450 aromatase and estrogen receptor, shows that human thyroid gland has a role in both estrogen synthesis and intracrine / paracrine estrogen responsiveness [14]. This indicates a possible association between breast and thyroid cancers. There was a positive association between anti TPO antibodies levels and the risk of breast cancer in our study. Autoimmune thyroid diseases have been positively associated with breast cancer risk in several cross-sectional studies [15] but the only previous prospective study, including only 15 cases, showed that the prediagnostic presence of anti TPO antibodies was not related to the subsequent risk of breast cancer [16]. It is unclear whether the presence of anti TPO antibodies in serum from patients with breast cancer is related to an increased risk following anti TPO antibodies related conditions, or if it is a general autoimmune response to the malignancy [17]. Our results suggest that the existence of a biological link between breast cancer and serum anti TPO antibodies in women. However, further studies on large population are required to substantiate this association. 5. CONCLUSION The increased serum anti TPO antibodies levels in breast cancer patients shows an association between these two organs. Whether it is due to autoimmune response of the body to malignancy still remains to be clarified. REFERENCES 1. Breast cancer in developing countries. Lancet 2009; 374: Tfayali A, Temroz S, Marod RA, Shamseddine A. Breast cancer in low and middle income countries ; an emerging and challenging epidemic. J Oncol 2010; Kim JJ, Champan Davis E. Role of Progesterone in endometrial cancer. Semin Reprod Med 2010; 28: Lewis Wambi JS, Jardon VC. Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? Breast cancer Res 2009; 11: Fucic A, Gamulin M, Ferencic Z, et al. Environmental exposure to xenoestrogens Intl. J Chem Pharm Res 2013;2(7):

5 and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain. Environ Health 2012; 11: Silva JM, Dominguez G, Gonzalez Sanccho JM, et al. Expression of thyroid hormone receptor / erba genes is altered in human breast cancer. Oncogene 2002; 21: Rebbaa A, Chu F, Davis FB, et al. Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent. Angiogenesis 2008; 11: Sar P, Peter R, Rath B, Das Mohapatra A, Mishra SK. 3, 3'5 Triiodo L thyronine induces apoptosis in human breast cancer MCF-7 cells, repressing SMP30 expression through negative thyroid response elements. PLoS One 2011; 6: Cestari SH, Figueiredo NB, Conde SJ, et al. Influence of estradiol and triiodothyronine on breast cancer celllines proliferation and expression of estrogen and thyroid hormone receptors. Arq Bras Endocrinol Metabol 2009; 53: Guigon CJ, Kim DW, Willingham MC, Cheng S-Y. Mutation of the thyroid hormone receptor- â in mice predisposes to the development of mammary tumors. Oncogene 2011; 28; 30: Ferlay J, Bray F, Sankila R and Parkin D: GLOBOCAN 2002.Cancer incidence, mortality and prevalence worldwide, Version ; IARC Press; Lyon. 12. Giani C, Fierabracci P, Bonacci R, Gigliotti A, Campani D, De Negri F, et al. Relationship between breast cancer and thyroid disease; relevance of autoimmune thyroid disorders in breast malignancy. J Clin Endocrinol Metab 1996; 81: Davies TF. The thyrotrophin receptors spread themselves around. J Clin Endocrinol Metabol 1994;79: Dalla Valle L, Ramina A, Vianello S, Fassina A, Belverdere P, Colombo L. Potential for estrogen synthesis and action in human normal and neoplastic thyroid tissues. J Clin Endocrinol Metab 1998; 83: Turken O, Narin Y, Demirbas S, et al. Breast cancer in association with thyroid disorders. Breast Cancer Res 2003; 5:R Kuijpens JL, Nyklictek I, Louwman MW, Weetman TA, Pop VJ, Coebergh JW. Hypothyroidism might be related to breast cancer in post-menopausal women. Thyroid 2005; 15: Smyth PP. The thyroid, iodine and breast cancer. Breast cancer Res 2003, 5: Intl. J Chem Pharm Res 2013;2(7):