DOI: https://doi.org/10.53350/pjmhs22167594 ORIGINAL ARTICLE 594 P J M H S Vol. 16, No. 07, July 2022 Insinuation of Extrapolative Factors of Diagnostic Importance in Breast Cancer Patients Experiencing Thyroid Dysfunction SAMINA MALIK 1 , MAHWISH AROOJ 2 , SULAYMAN WAQUAR 3 , NAVEED SHUJA 4 , ARIF MALIK 5 1 Professor and Head, Department of Physiology, University College of Medicine and Dentistry (UCMD), PhD Physiology student, Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore (UOL), Lahore, Pakistan 2 Professor of Physiology and Principal, UCMD, UOL 3 PhD student, IMBB, UOL, Senior Lecturer, Minhaj University 4 Associate Professor, Department of Biochemistry, Lahore Medical and Dental College, LMDC, Lahore Pakistan. 5 Professor and PhD Supervisor, IMBB, UOL Corresponding author: Samina Malik, Email: drsemymalik58@gmail.com, Cell: +92-301-8652128 ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women and now regarded as the commonest cancer overall. Over 2 million new cases were diagnosed in 2018, accounting for almost 25% of cancer cases among women. The main objective of the study is to find the insinuation of extrapolative factors of diagnostic importance in breast cancer patients experiencing thyroid dysfunction. Materials and methods: This correlational study was conducted on Jinnah Hospital patients with the permission of ethical committee of the hospital and consent of the patients. The data was collected from 88 cases and 50 controls. All the patients who had a definite diagnosis of BC along with, hyperthyroidism, hypothyroidism, autoimmune thyroid disease (AITD), or thyroid cancer were included in this study. The study population was divided into three comparative groups: (1) controls (n = 50), (2) BC cases with hypothyroidism (n = 27), and (3) BC cases with hyperthyroidism (n = 61). Results: The mean age was 47.325±4.59 years for controls, 51.59±8.59 years for the hypothyroid cases, and 50.59±5.58 years for the hyperthyroid cases. The mean systolic blood pressure (SBP) for controls, hypothyroid and hyperthyroid was 121.25±6.58 mmHg, 98.259±8.59 mmHg and 129.65±7.59 mmHg respectively. The P-values less than 0.05 were considered to be significant (table 01). The demographic and hematological data of control, hypothyroid and hyperthyroid groups was tabulated. A positive correlation of breast cancer in women with hyperthyroidism and a slightly negative correlation in women with hypothyroidism was found. Conclusion: There appears to be an association between the thyroid function level and breast cancer risk. It can be extrapolated that anxiety associated with hyperthyroidism may play a role in stress induced BC. Therefore, thyroid function should be monitored in patients at risk of BC. Keyword: Breast cancer, Thyroid, Dysfunction, Hypothyroidism, Hyperthyroidism, Anxiety. INTRODUCTION Breast cancer (BC) is the most common malignancy in women and the now the most common cancer overall overtaking the lung cancer according to World Health Organization’s 2021 statistics [1, 2]. Over 2 million new cases were diagnosed in 2018, accounting for almost 25% of cancer cases among women. Although hereditary and genetic factors account for 5–10% of BC cases [3], nonhereditary factors are more commonly involved in geographical and ethnic differences in incidence [4]. The relationship of BC with thyroid disease (TD) has been widely investigated. However, data are still controversial and, although almost every form of TD, including autoimmunity disorders and thyroid cancer, has been identified in association with BC, no convincing evidence exists of a causal role for TD in BC [5]. Hypothyroidism is the most common hormone deficiency. The severity of hypothyroidism varies significantly, and it has a variety of end organ effects. Because of both the nonspecific symptoms of hypothyroidism and the similar symptoms and morbidities associated with malignancies and their treatment, hypothyroidism can often go undiagnosed and untreated in patients with cancer [6]. Failure to adequately manage both overt and subclinical hypothyroidism can have serious consequences, hence the recognition of its presence is crucial for the successful treatment of cancer patients. Hypothyroidism is commonly noted in older women because of the prevalence of autoimmune thyroiditis [7]. Younger women and men are now being diagnosed secondary to other important causes, including previous thyroid, brain, and spinal cord surgery and irradiation and medications. Hypothyroidism is easily treated with thyroxine (T4) replacement. Unfortunately, suboptimal dosing is common [8]. Breast cancer (BC) is the most common type of cancer in females, occurring in 20% of the female population world-wide, and is the main cause of tumor-related death in women. Studies have shown that BC is closely related to the endocrine system [9]. The thyroid is an important part of the endocrine system and secretes thyroid hormone (TH), which plays a vital role in the growth, development, and metabolism of cells and tissues. As pituitary hormones target both breast and thyroid tissues, there may be a correlation between BC and thyroid disorders [10]. Hardefeldt et al. found that there was significant evidence of an increased risk of BC in patients with presence of anti-thyroid antibodies, while they also found that there was no significant evidence of an increased risk of BC in patients with hypothyroidism and hyperthyroidism [11]. But more high-quality prospective studies are needed to prove causal relationship between benign thyroid disease and BC. However, the relationship between BC and thyroid diseases, such as hyperthyroidism, hypothyroidism, autoimmune thyroid disease (AITD) and thyroid cancer, is still not well understood [12]. Angelousi and colleagues demonstrated that TH promoted the proliferation of breast cancer cells in vitro, while hypothyroid function resulted in a lower incidence of lymph node metastases. Recent studies have suggested that TH may play a positive role in the cause and development of BC at a cellular level. However, Hercbergs et al. found no evidence that TH causes BC in the clinical setting. Despite numerous studies having investigated the association between thyroid dysfunction and BC, the exact relationship and molecular mechanisms involved remain unclear. Further studies examining the prognostic role of TH in BC are thus warranted [13-14]. According to epidemiological statistics, the cumulative incidence of developing a second malignancy in a patient with thyroid cancer is 16% at 25 years. Previous studies have shown that there is a unidirectional or bidirectional association between thyroid cancer, breast cancer and renal cell carcinoma [15]. A unidirectional association is defined as a primary cancer that increases the relative risk of subsequent cancers, while a bidirectional association indicates that there is a two-way relationship or mutual relationship between two cancers, and has nothing to do with the subsequent occurrence. Thyroid cancer survivors have a high incidence of breast cancer, and breast cancer survivors have a high incidence of thyroid cancer [16].