Journal of Surgery

Introduction

Breast malignancy is the most common cancer in females and the second death-leading etiology [1]. In 2022, there were 2.3 million women diagnosed with breast cancer and 670,000 deaths globally [2]. An understanding of possible associated causes or correlations could provide a better understanding of dealing with this highly concerning disease. In Kuwait, cancer is one of the most prevalent health concerns [3-5]. As per the latest epidemiological data in Kuwait, cardiovascular diseases are identified as the first cause of mortality (61.4. per 100,000 population), followed by cancer (20.8 per 100,000 population) [3-5]. Among the newly reported cancer cases in 2019, breast cancer ranks as the most common malignant neoplasm in females, accounting for 35.4% of Kuwaitis and 38.4 % of non-Kuwaitis [5]. Between 2010 and 2019, 26609 new cancer cases were documented in Kuwait. Of these, 5719 cases were breast cancer [5]. In 1896, Beatson utilized thyroid agent as a highly effective treatment agent for breast cancer metastasis, documenting the correlation between breast malignancy and thyroid gland activity [6,7]. According to Loeser and Ellerker’s 1950 study, breast cancer was observed to develop more commonly in hypothyroid females than in ones with hyperthyroidism [6]. Moreover, Kapdi et al. reported the causal relationship between hypothyroidism and elevated risk of breast carcinoma in 1976 [6]. Numerous studies documented a significant association between the probability of breast neoplasms and antithyroid peroxidase autoantibodies [6]. Both mammary and thyroid glandular cells had similar pathological and physiological mechanisms that involved iodine cellular storage, transport by natrium-iodide symporter, and oxidization [6,7]. At a molecular level, the expression of thyroid hormone receptors on mammary glands and the plasma membrane of breast cancer cells can interpret the association between thyroid and breast tissue pathology [6]. Multiple studies reported the association between breast cancer cases and thyroid gland activity, especially hypothyroidism [6-8].

Our study aimed to evaluate the pattern of hypothyroidism among patients in Kuwait undergoing cancer surgery for various types of breast cancer. We planned to study and determine the risk of hypothyroidism in breast cancer patients who were either untreated or treated with surgery, radiotherapy, and chemotherapy.

Materials and Methods

This study was approved by the Standing Committee for Coordination of Health and Medical in the Ministry of Health of Kuwait (Research official number 2199/2022). The database was searched for English literature that assessed the association between breast malignancies and hypothyroidism.

Study Design

This study is a retrospective, cohort analysis using data from medical documents of governate and private hospitals in Kuwait. The governate hospitals included the Kuwait Cancer Control Centre (KCCC) as well as all major General hospitals in Kuwait (Adan, Mubarak, Amiri, Jahra, Farwaniya, Jaber Al-Ahmad, Ahmadi Kuwait Oil Company (KOC), and Armed Forces

Hospital). Moreover, private hospitals were involved in the study. These compromise Al-Salam, Hadi, Royal Hayat, Taiba, New Mowasat, Al Seef, and Dar Al Shifa hospitals.

Study Population

The study population included patients who underwent breast cancer surgery and their level of hypothyroidism. The extracted data was from 10 years, from January 2010 to December 2019. A total of 5860 patient’s information was included in the study. Our retrospective research was based on inclusion and exclusion criteria. The inclusion criteria include females, aged 35 years or older, operated on for breast cancer, and diagnosed between January 2010 and December 2019. All these patients were operated in governate and private hospitals. On the other hand, we exclude females with hyperthyroidism at the time of breast cancer and females aged less than 35 years. The retrieved information included menopausal status, age at diagnosis, thyroid hormone level, recurrence of breast malignancy, follow-up with treating physician, surgery type, exposure to chemotherapy and radiotherapy, HER-2 status, and histologic grade. So, our exclusion criteria involved hyperthyroidism, unknown tumor stage, and unknown primary surgery or radiotherapy. Statistical analysis and study outcome assessment were done by SPSS software.

Results

A total of 5860 patients were included. The results of hypothyroidism distribution in different types of breast carcinoma are shown in Table 1. In patients with hypothyroidism, Invasive Ductal Carcinoma (IDC) was highly documented (93% of total cases represented IDC with a p-value of 0.181).

Table 1: Distribution of hypothyroidism in different cancer types.

According to the Kuwait Cancer Registry, Invasive ductal carcinoma was the most frequent cancer morphology accounting for about 84% [5].

A positive association between the risk of invasiveness and hypothyroidism in breast carcinoma cases was reported in Table 2. The risk of invasive breast malignancies in patients with hypothyroid disease accounts for 96% with a risk ratio of 2 (95% CI 1.0-3.9, p-value 0.031).

Table 2: Risk ratio of hypothyroid in invasive carcinoma.

As a result of the high invasiveness status, the relationship between the hypothyroid breast cancer patients and multiple therapeutic modalities is reported. It is noticed that breast surgery was the primary treatment method to be performed in these cases. The various treatment methods in hypothyroid patients with breast carcinomas are statistically presented in Table 3. The combination of surgery and chemotherapy agents is the most utilized treatment method (25.5%, p-value of 0.04).

Among risk estimation, the odds ratio indicated an elevated risk of invasive breast malignancies among hypothyroid cases (OR 2.019, 95% CI 1.047-3.891).

Table 3: Distribution of hypothyroidism in different therapeutic.

The statistical significance was identified between hypothyroidism and the risk of invasive breast cancer by Pearson Chi-Square (value of 4.690, Sig. 0.030). Furthermore, the Chi-Square test demonstrated a strong correlation between hypothyroid status and breast malignancies (value 7.580, Sig. 0.181).