Author name:
هبة جمعة عبد الخالق
Supervisor name:
خضير جاسم صبيح الرواق
Abstract:
Background : Breast cancer is the most common malignancy in women worldwide and the leading type of cancer among Iraqi women with a rapidly rising incidence. It is necessary to have non - invasive and sensitive methods for early detection. Alkaline phosphatases (ALP) are a group of hydrolase enzymes that catalyze the hydrolysis of phosphate esters in an alkaline environment. The increase in serum level of ALP is usually associated with certain diseases, including malignancy. Malignancy mayraise ALP level by several mechanisms, therefore, changes in serum ALP level may be useful in the diagnosis and follow up of breast cancer. Aim of the Study : To assess the relationship between increased serum ALP level and the occurrence of metastasis in breast cancer patients, and to assess the possibility to use this enzyme as a biomarker for the detection of metastasis in breast cancer.Methodology : This study is a case - control study conducted in Oncology Teaching Hospital in Medical City - Baghdad from 1st of December 2017 through 30th of April 2018 and included 140 patients with breast cancer.70 of them had metastasis (Group A) and 70 had no metastasis (Group B).Blood samples were collected to determine serum ALP level..Results : Age of participants ranged from 25 - 71 years, with mean age of 50 years, and 50.4% of them had disease stage IV. Mean ALP level of Group A (metastasis group) was (320.5 ± 254.9)IU/L with 15.7% of them within normal range, whereas the mean ALP level in Group B (control group) was (85.1 ± 34.9)IU/L with 85.7% within normal range. Statistical analysis have shown that there is statistically significant difference in the ALP level between the two groups. t(138)=7.65, P < 0.001.Conclusions : Serum Alkaline Phosphatase level is an important prognostic tool for monitoring of progression of breast cancer, and it could be used as a biomarker for detection of metastasis in breast cancer patients.Keywords : alkaline phosphatase, breast cancer, metastasis 1.1 IntroductionAlkaline phosphatases (ALP) are a group of hydrolase enzymes that catalyze the hydrolysis of phosphate esters in an alkaline environment. In healthy human adults, ALP is derived from certain tissues including bones, liver, placenta, intestines, and kidneys (Al - Mashhadani, Mukhlis and Al - Faraji, 2012). The increase in serum level of ALP is usually associated with certain diseases including hepatitis, intrahepatic cholestasis, extrahepatic bile obstruction, infiltrative liver diseases, and cancer. Higher levels of ALP are seen in more specific disease, such as primary biliary cirrhosis, primary sclerosing cholangitis, malignant biliary obstruction, hepatic lymphoma, and breast cancer.Therefore, changes in serum ALP level may be useful in the diagnosis and follow up of breast cancer (Singh et al., 2013). These enzymes are present on cell membrane outer layer, and their function is to catalyze the hydrolysis of the organic phosphate esters that are located in the extracellular space. Each catalytic site contains 3 ions made up of 2 zinc ions and one magnesium ion, which are considered important co - factors for the enzyme (Lowe and John, 2017). Alkaline phosphatases are considered true isoenzymes since they catalyze the same reaction throughout the different tissues of the body.They are classified into either tissue - specific or tissue - non - specific type.Tissue - specific type include alkaline phosphatases found in placenta, intestine, or germinal tissues. This means that they are present only in tissues where they are physiologically formed, and may occasionally 1contribute to the serum alkaline phosphatase in the circulation under certain circumstances. Tissue - non - specific alkaline phosphatase, on the other hand, is generally the main constituent of the circulating serum alkaline phosphatase, which gives it a particular clinical importance. It is formed mainly in bone, liver, and kidneys (Lowe and John, 2017; Millán, 2006).Breast cancer is the most common malignant disease in women worldwide (Stieber et al., 1992). It is considered the most common type of cancer in both developing and developed countries, and is the fifth cause of cancer mortality in the world (Ferlay et al., 2010). In Iraq it is the leading type of cancer among Iraqi women, accounting for one - third of the total registered female cancer patients in Iraq (Iraqi Cancer Board, 2010), with a rapidly rising incidence among Iraqi population (Al - Hashimi and Wang, 2014).Locally advanced breast cancer is usually diagnosed after the detection of a palpable mass within the breast. Symptoms may include pain (whether local or regional), bleeding, paresthesia or paresis. Breast cancer patients who are presented with locally advanced disease require management by a multidisciplinary team that utilizes diagnostic imaging, chemotherapy, surgical intervention, and pathological assessment. The outcome of treatment for each patient could depend on the level of integration of this multidisciplinary approach in addition to the experience of the team members. Coordination between those members is of particular importance in the management of those patients with locally advanced breast cancer, because those patients have a high risk ofrecuurence of the disease if no optimal treatment was provided. However, 2 the outcome of patients with locally advanced disease has improved recently with the routine use of chemotherapy. Before the routine use of chemotherapy there was a high rate of distant metastases and death among patients treated with mastectomy or radiation (Haagensen and Cooley, 1969).Breast cancer is classified histopathologically into either invasive ductal carcinomas (IDC), invasive lobular carcinoma (ILC), or not otherwise specified (NOS) (Viale, 2012). Intrinsic subtypes of breast cancer are described in Table 1 (Pudney et al., 2015).To investigate for the disease, a complete history is essential, followed by triple assessment which include physical examination, radiological investigation, and needle biopsy. It is preferred to use core biopsy rather than fine - needle aspiration since the core biopsy provides a histological diagnosis and can be used for differentiation between invasive and in situ carcinoma. Also it is possible to test for ER, PgR andHER2 status using biopsy specimen.
