The Etiology and Pathogenesis of Human Breast Cancer - Research Paper Example

? Breast Cancer Breast Cancer Like in many other developed countries, the incidence of breast cancer has been on the increase. In the U.S in particular, breast cancer incidence has been on the increase in the past twenty years. Despite the increasing incidence, the mortalities resulting from breast cancer are however on the decline largely due to technological advances and a host of other factors like increasing physical exercise and more informed lifestyles (SDSU, 2010). Although there exists disparities among women from different ethnic, racial and cultural backgrounds, the developments in research of breast cancer offer a promising solution to all affected. It has been reported that in the year 2006 in U.S approximately 274,900 cases of breast cancer were diagnosed with 61,980 of these cases being in situ carcinomas and the rest (212,920) being malignant breast cancers. Currently more than 2 million women in the United States have been diagnosed and undergone treatment of breast cancer. Gender has been reported as one of the greatest risk factors. Women are at a higher risk of developing breast cancer than men (SDSU, 2010). In the same statistics of 2006, only 1,720 men were reported to have breast cancer. This paper is going to focus on the anatomy and physiology of the breast and lay more emphasis on cancer of the breast. The breast is a mass of fatty, glandular and fibrous tissues that are attached to the chest wall by Coopera ligaments. They are positioned over the chest wall pectoral muscles (The Women’s health Resource, 2012). It lies on a region from the edge of the axilla to the edge of the sternum between the second and the sixth rib (SDSU, 2012). The normal breast consists of various tissues which serve a specific purpose. The tissues include fat, ducts, lymph nodes; lobules, lobes, and connective tissue that hold the whole structure together (Mayo Clinic, 2011). See figure1. The breast parenchyma has been divided into four quadrants which include the upper inner and outer quadrant and the lower inner and outer quadrant. Cancer has been noted to occur in the upper outer quadrant most of the time. Radiating from the nipple are roughly 15-20 lobes. The lobes are each surrounded by fibrous connective tissue and fat. These structures divide the lobe into many lobules. The lobule is lined by epithelial cells and is the basic structural unit of the breast (SDSU, 2012). The alveoli are the milk producing units of the breast and arise from the subdivision of the lobule by the fibrous connective tissue. When the milk has been formed within the alveoli, it flows into ducts which then coalesce into approximately 10-15 major ducts. Each of the lobes contains a single duct. These ducts then terminate at the nipple (SDSU, 2012). The nipple contains smooth muscle and openings of the lactiferous ducts. It is surrounded by the areolar which contains sweat glands, accessory mammary glands and sebaceous glands. These structures form tubercles when the woman is pregnant and during lactation they lubricate the nipple (Muller & Swenson, 2008). Notably, the amount of fat within the breast of woman determines its size. Generally the structures that produce milk within the female breast are largely the same. Older women who are past menopause tend to have more fat within their breasts and therefore have larger breasts compared to the younger women (Mayo Clinic, 2011). The blood supply of the mammary gland arises from a number of arteries which include branches of internal thoracic artery, intercostals arteries and axillary arteries. The deep veins of the breast then drain into the correspondingly named veins. The blood supply connection that is present between the vertebral plexus and the intercostals veins account for most of the metastasis to the nervous tissue and bones. The lymphatic drainage of the breast plays a great role in the metastasis of cancer. A great potion of lymph from the breast drains through the axillary nodes (Muller & Swenson, 2008). Other lymph is drained through the apical nodes of the axilla, the parasternal nodes, contralateral breast via connections that cross the median plane, the subhepatic and subperitoneal plexuses (Muller & Swenson, 2008). The breast is innervated by the anteromedial and anterolateral branches of the thoracic intercostals nerves (T3-T5). Supraclavicular nerves from the cervical plexus also innervate the lateral and upper parts of the breast. Research has shown that most of the nipple sensation is derived from the a branch of T4 -lateral cuteneous branch (Gabriel, 2011). Cancer is basically a process whereby normal cells undergo certain changes that result in their conversion into cells that multiply at a high rate to the extent that the process ends up being out of control (SDSU, 2012). Cancer of the breast has been noted to occur on the upper outer quadrant of the breast. Certain factors are closely associated with development of breast cancer. These factors are primarily genetics and hormones factors. There exist several types of breast cancer. They include noninvasive breast cancer, and the invasive breast cancer. The noninvasive breast cancers include ductal carcinoma in situ and lobular carcinoma in situ. Ductal carcinoma accounts for approximately 15% of the new cases of breast cancer in the U.S and is one of the most common types of breast cancer. This cancer involves the uncontrolled proliferation of cells that are located within the ducts of the breast. Lobular carcinoma is another example of a noninvasive breast cancer. The cells that line the milk producing lobules of the breast undergo certain abnormal changes (SDSU, 2012). Among the invasive types of breast cancer are infiltrating/invasive ductal carcinoma, infiltrating/invasive lobular carcinoma, tubular carcinoma, medullary carcinoma, Mucinous carcinoma, metaplastic carcinoma, invasive cribriform carcinoma, invasive papillary carcinoma, and invasive micropapillary carcinoma (SDSU, 2012). All these cancers are influenced by either genetic or hormonal factors. With reference to the physiology of the human breast, the microenvironment of the breast has the capacity to influence the events that are closely associated with development of cancer. For a long time the role of hormones in the initiation and or progress of cancer in human breast cells has elucidated. It has been the popular position that hormones are able to influence the risk of breast cancer by controlling the rate of mitosis within the epithelial cell of the breast (Adami, et al., 1995). The high mitotic rates of the epithelial cells may result in increased chances of mutation occurring and being replicated across multiple sites before the repair mechanism sets in. Recent studies have revealed that IGF-1 and prolactin may be closely associated to the risk of breast cancer. IGF-1 (Insulin growth factor -1) is closely associated with breast cancer in premenopausal women and prolactin is closely associated with cancer in postmenopausal women (Key, & Verkasalo, 1999). Studies that focused on the rate of mitosis of the epithelial cells of the breast of premenopausal women have revealed that mitosis occurs during the whole menstrual period. During this period there is a peak in the serum levels of both progesterone and estradiol. In other separate studies estradiol has been demonstrated to be a mitogen and is associated with factors that initiate breast cancer in humans. Progesterone alone has been proven to have no effect on breast tissue in terms of mutagenicity in human breast cancer tissue that had been grafted into mice. However the possibility that progesterone, while in ideal physiological conditions can have mutagenic effects on human breast tissues cannot be ignored (Key, & Verkasalo, 1999). It is therfore possible that estradiol acting alone may increase the risk of breast cancer but the hormone progesterone may as well augment the effect of estradiol on the epithelial tissue of the human breast in premenopausal women (Key, & Verkasalo, 1999). Apart from its effect on the epithelial tissue of the human breast, estradiol has been implicated as having the ability to increase risk of breast cancer by damaging DNA directly. Estradiol has some metabolites that are free radicals and have the ability to destroy DNA directly (Key, & Verkasalo, 1999). One of these metabolites is 4-hydroxyestradiol. This radical effect of estradiol is based on studies that have been conducted in hamsters and a need for more investigation to gain more insight into the issue is necessary (Key, & Verkasalo, 1999). The microenvironment can either increase or reduce the rate of these events that are associated with cancer development (Pai, et al., 2009). Serotonin is a hormone that has been identified to play a major role in the physiology of the breast. The hormone specifically regulates the homeostasis of the epithelial tissue. Complex alteration of the serotonin system within the mammary gland is responsible for breast cancer episodes (Pai, et al., 2009). In a study conducted to demonstrate the complex alterations of serotonin system, the biosynthetic capacity of serotonin was analyzed within human breast tumor tissue microarrays. Immunohistochemistry for TPH1 (tryptophan hydroxylase 1) was used in the analysis of the breast tumor tissue. The study went further to compare the serotonin receptor expression, 5-HT effects on the phenotype of breast cancer cells, and signal transduction in the transformed human breast cells and the non transformed human breast cells. The study found out and concluded that in the normal mammary gland, 5-HT acts as a physiologic regulator of involution and lactation. It achieves this by favoring cell death and growth arrest. In the case of the human breast cancer, this system of control by the 5-HT has been subverted in several ways. During progression, the TPH1 expression was noted to undergo a nonlinear change accompanied with increased expression seen during malignant progression. Within the human breast cancer cells, the well regulated 5-HT receptor pattern is dysregulated. This results in the suppression of some isoforms and the expression of others. The change in receptor expression was noted to be accompanied with altered downstream signaling of the receptors (5-HT) in the breast cancer cells in humans. As a result there is development of resistance to 5-HT induced apoptosis and increased proliferation. Apart from the serotonin hormone, other factors are thought to influence the occurrence of breast cancer in the human female breast. There is evidence that the non lactating human breast plays a fundamental role in the in the factors that contribute to the development of breast cancer (Mills, et al., 2011). In a study conducted to compare the transportation of exogenous substances (drugs) in ductal fluid and compare their concentration to those of the lactating woman revealed interesting information (Mills, et al., 2011). Two exogenous substances (caffeine and cimetidine) were used for the study. Fourteen participants ingested the two substances and had blood drawn from them. The participants also underwent ductal lavage over a 12 hour period (Mills, et al., 2011). This was to enable the investigators to measure the levels of the two drugs in the blood and the ductal fluid. IT was noted that the levels (concentration) of the two drugs were significantly lower both in blood and ductal fluid in the non lactating breast when compared to the lactating breast. The study reveals substantial differences between the physiology of the lactating and the non lactating breast. Perhaps with further research into the physiology of the non lactating breast will help elucidate the factors that are associated with the initiation and progression of the disease (Mills, et al., 2011). In conclusion, breast cancer has been a major cause of mortality among the U.S women but with the improving technology the mortality rate is reducing. Many hormones have been associated closely with increasing the risk of breast cancer including serotonin, estrogen, etradiol, and progesterone. These hormones are believed to contribute to increasing the risk of breast cancer by increasing the rate of mitosis of the epithelial cells of the breast. Appendix Figure 1: Structure of the human female breast. Sourced from the Mayo foundation for Medical education and Research. (Retrieved from: http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001&slide=2 ) References Adami, H.O., et al.(1995). The aetiology and pathogenesis of human breast cancer. Mutation Research, 333 (1), 29-35. Gabriel, A. (2011). Vascular anatomy and innervations of the breast. Retrieved from: http://emedicine.medscape.com/article/1273133-overview#aw2aab6b3 Key, J.T., & Verkasalo, P.K. (1999). Endogenous hormones and the aetiology of breast cancer. Breast Cancer Research, 1(1), 18-21. Mayo Clinic (2012). Women’s health: Female breast anatomy. Retrieved from: http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001&slide=5 Mills, D., et al. (2011). The physiology of the humans breast: An exploratory study. Journal of Physiology and Biochemistry, 67(4), 621-627. Muller, R., Swenson, C. (2008). Chapter 7: Vessels, lymphatic drainage and the breast. Retrieved from: http://www.dartmouth.edu/~humananatomy/part_2/chapter_7.html Pai, et al., (2009). Altered serotonin physiology in human breast cancer cells favors paradoxical growth and cell survival. Breast Cancer Research, 11(6), 1-17. SDSU (2012). Anatomy and pathology of the breast. Retrieved from: http://qap.sdsu.edu/education/bcrl/Bcrl_anatpath/bcrl_anatpath_index.html Read More