Breast Cancer - Research Paper Example

? Breast cancer Contents 2. Introduction 3. Risk factors for breast cancer 3 Unchangeable risk factors for breast cancer 3.2. Changeable risk factors for breast cancer 4. Pathophysiologyof and classification of breast cancer 5. Prevention and treatment of breast cancer 6. Conclusion 7. References: 1. Abstract Breast cancer is a major cause for morbidity and mortality of women worldwide. This is condition predominantly affecting women and especially women in western countries or nations that accepted modern lifestyle of living. It is found that modern ways of living and diet are one of the most important factors that increase the risk for breast cancer in countries with modern way of living. There are many studies and intensive research is underway in order to identify the most important factors that are the reason for the constant increase of the incidence of breast cancer in the last several decades. The results and information’s from this research should help us reduce the morbidity and mortality from breast cancer and increase the self-awareness of the general population about the risks for this disease. In this study we will conduct a systematic research on the risk and other factors that are the most important factors in the etiology of breast cancer and also we will discuss the challenges of effective screening and treatment of breast cancer. 2. Introduction Breast cancer is malignant neoplasm that is originating from the tissues of the breast. It has significance as one of the most common cancers in the population that almost exclusively affects the female population, however in small percentages this malignancy is present in the male population also (less than 1% of all cases of breast cancer) (Florescu et al. 2011). Breast cancer is the most common type of invasive malignancy that affects women and contributes up to 23% of all invasive cancers that affect female population worldwide. It is registered that in year 2008 13.7% of cancer mortality in the female population in the world was caused by breast cancer or 6% of all cancer mortality worldwide (men and women) was caused by breast cancer (GLOBOCAN 2008). These numbers are alarming and show that breast cancer has severe impact on the global morbidity and mortality especially on the female population. It is also alarming that incidences of breast cancer are constantly increasing during the last three decades and this tendency is maintained till the resent day (Louwman et al 2008). It is believed that this is caused by the modern way of life and the changes that appeared in the habits and diets of modern way of living, changes in the reproductive behavior of the female population and other factors (Dignam et al 2003). This fact can be elaborated more clearly if we understand that the incidence of breast cancer is higher in western, developed countries and in countries that accept western way of lifestyle. For example incidences of breast cancer in population of 100 000 in western Europe is 78, in North America is 90 and these rates are significantly higher when compared to eastern Asia with 18 cases per 100 000 population, in sub-Saharan Africa 22 etc. (Stewart and Kleihues 2003). United States has the highest incidence of breast cancer in the world with 128 new cases of breast cancer on 100 000 women and in United States breast cancer is the second most common cancer after the skin cancer and the second most common cause of cancer mortality after lung cancer (American Cancer Society 2007). As we can see from the above statistics breast cancer has significant effect on the mortality in the population worldwide but especially in the developed countries. 3. Risk factors for breast cancer 3.1. Unchangeable risk factors for breast cancer There are many factors that is believed are the risen for the increase of the incidence of breast cancer in developed countries. In order to understand these factors we will look at the risk factors that are found to be associated with increased incidence of breast cancer. - As we can conclude from the above the primary risk factor for breast cancer is female gender. Incidence of breast cancer in males is less than 1% from the general incidence of breast cancer which means that breast cancer almost exclusively affects female population. However breast cancer in male population is also present and it tends to be associated with higher mortality compared to female population (Florescu et al. 2011). - Another risk factor for this malignancy is age. Breast cancer is rare in females below 25 years and has significant increase in incidences after age of 50 to 55 with almost half of all cases in population above 65 years old. We can understand the importance of advancing age in women as a risk factor for breast cancer if we know that in women of 40 to 49 years old, there is a 1 in 68 risk of breast cancer and this risk is much higher in the group of women with age between 50 to 59 where that risk is 1 in 37 women. (Goss et al. 2011). With aging of the general population in western countries this factor gains greater importance. - Family history of breast cancer is also very important risk factor for developing this malignancy. In a study conducted by Madigan et al. 1995 it was found that family history contributes for about 9% of all cases of breast cancer. There are a number of genes that when are present in mutated or inactive form can increase the risk of developing breast cancer and are associated with conditions called Hereditary breast-ovarian cancer syndromes (HBOC). There are many gene mutations that are identified as a risk factor for developing breast cancer (TP53, PTEN, CDH1 etc.) but the most common of all known genes mutations associated with breast cancer are BRCA1 and BRCA 2 genes (Morris et al. 2010). It is estimated that presence of BRCA mutation increases the probability for developing breast cancer during life time from normal 12 % to 60 % in women with present high risk mutation. Mutations of these genes also increase the risk of developing cancer in male population also (Kurian et al. 2010). However, these mutations are very rare and are found in only 4% of the population with breast cancer which means that inheritance of breast cancer susceptibility is mutagenic and depended on a combination of genetic and environment factors (Lacroix and Leclercq 2005). - It is also found that people with history of previous breast, ovarian, uterine, or bowel cancer has increased susceptibility to develop breast cancer (Margolese et al. 2000). This means that people with previous history of cancer morbidity are at increased risk of developing breast cancer also. 3.2.Changeable risk factors for breast cancer - There are other factors that are found to have effects on the incidence of breast cancer. Some of them are dietary factors or changes in the diet in the modern lifestyle as a factor for increased incidences of breast cancer. Alcohol is found to be na important risk factor for breast cancer in women (Room et al. 2005). The effect of alcohol is significant and dependent on the level of alcohol consumption. One study conducted on one million women in United Kingdom found that drinking one alcoholic beverage a day increases the incidence of breast cancer by 11 new cases per 1000 of women population. In the same study was found that taking 4 alcoholic beverages a day increases the incidence of breast cancer on 44 new cases per 1000 of population (Allen et al. 2009). It is found that 6% of all breast cancers in United Kingdom are as a result of alcohol consumption by women. - Increased saturated fat intake and obesity are also factors that are found to have significance in developing breast cancer, especially in western countries. There are studies that show that low fat diets can reduce the incidence of breast cancer in women and vice versa high fat diet increases the risk for breast cancer (Chlebowski et al. 2006). In the same time obesity and extra weight is also a factor that is found to increase the incidence of breast cancer in women. Heather et al. 2006 found that increasing of body weight by 10 kg or more after menopause increases the risk for breast cancer for 18%. The same authors found that actual weight loss after menopause is significantly reducing the risk for developing this disease. Other dietary factors are also identified like vitamin D deficiency, Iodine deficiency, specific national diets etc. (Nelson 2006) (Venturi 2001). - There are other factors like changes in the lifestyle that are found to have significant influence on the rates of breast cancer. It is found that increased levels of estrogen are associated with increased risk for developing breast cancer. In other hand increased levels of progesterone are associated with decreased risk for breast cancer (Yager and Davidson 2006). Changes in modern lifestyle induces factors that cause prolonged exposure to elevated endogenous estrogen, changes like not having children, delaying the first pregnancy, avoidance of breastfeeding, early menarche and late menopause and other factors. Delay in first pregnancy and avoidance of breastfeeding have been found as significant factor for breast cancer (McTiernan and Thomas 1986). Women who had their first child after age 30 have double risk of breast malignancy when compared to women with first pregnancy before age of 25 (Newcomb et al. 1994). Use of hormonal replacement therapy is also found to be a risk factor. There are studies that show linear correlation between the duration of hormone replacement therapy and breast cancer. In the same time combination of progesterone and estrogen does not results in decrease in the risk for breast cancer (Colditz ET AL. 1995). Hormone contraception is also found to have slight effect on increased risk for breast cancer and this risk is greater if the use of this contraception is started at earlier age (WHO 1999). There are other mentioned risk factors like carcinogeous materials, special diets, diathesis etc but the above mentioned are found to have most significant effect on the increased risk for developing this malignancy. 4. Pathophysiologyof and classification of breast cancer Breast cancer, as any other form of cancer is a result of combination of genetic and environmental factors that results in formation of cancerous cells. Normal tissue cells divide under controlled conditions and communicate with the surrounding cells to stop dividing when the tissue is formed. Mutations of many genes have been found that can cause breast cancer and cancer in general (p53, BRCA 1, BRCA2, RAS, WNT, MYC and other genes). Mutations of many genes are needed to occur in order carcinogenesis to occur (Knudson 2001). As a result of these mutations cancers cells start dividing uncontrollably and start to invade the surrounding tissues. Once the cancer cells start to divide, the process of clonal evolution ensures growth and selection of most aggressive and resistant cancer cells that manage to avoid the mechanisms of immunity (Merlo et al. 2006). There are several forms of breast cancers that are classified based of the characteristics of growth and their location. This is important because treatment algorithms relay on this classification in order to implement the most effective treatment (Gonzale et al. 2007). Based on their histological type most of the breast cancers belong in three groups: Invasive Ductal carcinoma (accounting for 55% of breast cancers), Ductal carcinoma in situ (13%) and Invasive lobular carcinoma (5% of all breast cancers) (Eheman et al. 2009). There are other histological types of breast cancers that are present in much smaller percentages. Invasive ductal carcinoma is the most common type of breast cancer and is originating from the milk ducts or lactiferous ducts within the breasts. There are two different forms: invasive and carcinoma in situ. Invasive form of ductal carcinoma is the most common type of breast cancer (Eheman et al. 2009). On examination it has firm consistency and has a tendency to invade the surrounding tissues of the breasts. This type of carcinoma also has a number of subtypes (mucinous, papillary, cribriform etc) and the prognosis and effectiveness of treatment is different in different subtypes. Ductal carcinoma in situ on the other hand is the most common form of noninvasive breast cancer. It is cancer that still hasn’t pierced the basal membrane of the cells and is confined within the milk ducts in the breasts. It is actually called precancerous stage and by some authors is not classified as cancer. However, if left untreated ductal carcinoma in situ will develop into invasive ductal carcinoma (Welch et al. 2008). Invasive lobular carcinoma is originating from the the milk producing glands (lobules). There are several forms of this type of cancer (alveolar, solid, mixed etc.) and all of them have different prevalence’s, however in total this type of cancer accounts for only 5 to 10 % of all invasive breast cancers (Boughey et al. 2009). As we mentioned above classification of breast cancers is important in order to assess the most effective therapy, however other factors like cancer size, involvement of lymph nodes, metastases and other factors are also important in choosing the most appropriate treatment. This is why a staging of the breast cancers was developed. This staging is based on the TNM system where T stands for tumor size, N for presence of involvement of lymph nodes and M presence of distant metastases. Based on this system breast cancer is divided in 6 stages and every stage has different rate of predicted survivability. Based on this classification 5 year survival rate was estimated on 50 000 patients with breast cancer and the results are presented in table 1. (Kumar et al. 2007). Breast cancer stage (AJCC 5th edition) 5-year overall survival of over 50,000 patients Stage 0 92% Stage I 87% Stage II 75% Stage III 46% Stage IV 13% Table. 1 – Staging of breast cancer and survivor rates. However these results do not include other factors that are important for the prognosis and treatment of breast cancer. Another important factor that influences the treatment and prognosis of breast cancer is the receptor status of the cancer. Cancer cells of breast cancer may be influenced by hormones or other messengers which may have significant effect on their growth and treatment. Breast cancers cells may or may not have estrogen receptors, progesterone receptors or HER2/neu receptors (Christos and Pusztai 2009). These characteristics may be used for the treatment or classification of this disease. For example estrogen receptor positive breast cancers may be treated with estrogen blocking drugs (tamoxifen for example) that reduces the growth rate of the cancer. Tamoxifen can also be used as prevention in women with increased risk factors for developing breast cancer also (Fisher et al. 1998). 5. Prevention and treatment of breast cancer There are many treatments available to treat breast cancer, however the most effective method of treatment is still prevention and screening. Early detection, at an earlier stage will result in increased survivability and better prognosis for the patient, as it was shown in table 1. Clinical or self breast exam is at the core of the screening program for breast cancer. This exam involves manual searching and feeling of the breasts for presence of lumps or other abnormalities like change in color, retraction of the nipple, discharge from the nipple etc. (Kosters and Gotzsche 2003). Another effective method of screening is mammography, where soft x-rays are used in order to examine the breasts for presence of calcifications, cancer masses or other changes. It is found that mammographic screening is reducing the incidence of breast cancer by 15 percents, mostly by early detection and treatment at early stages (Gotzsche and Nielsen 2009). In order to mammography to have effect it is recommended that serial mammography’s are conducted every 2 years in women of age between 50 and 74 (Gotzsche and Nielsen 2009). In families with history of breast cancer genetic testing for presence of genetic mutations is also recommended in order to conduct preventive measurement (O'Connor et al. 2009). As we mentioned screening is the most effective treatment of breast cancer, however when breast cancer is not recognized early there are treatments protocols that are designed in order to achieve most effective treatment. Those protocols include surgery, medication, radiation therapy, chemotherapy and other methods. These treatments may be combined between each other depending on the stage and type of the breast cancer. This is why multidisciplinary approach must be incorporated with wide mechanisms of diagnosis and also treatment in order to achieve the best effects (Saini et al. 2011). 6. Conclusion As we can conclude from the above text there are many factors that predispose to developing breast cancer. Identification of these factors and implementation of preventive measurement are most important in reducing the incidence and prevalence of breast cancer. Incidences of breast cancer are rising constantly and this is connected with the modern way of living and lifestyle. Increasing the self-awareness and knowledge of modern women about the risks for breast cancer will result in significant reduction of incidences of breast cancer. 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