Is There a Light at the End of the Tunnel with Breast Cancer - Research Paper Example

? [Type the document [Type the document sub [Pick the [Type the company pc Breast Cancer Pathology & Human Biology Introduction Breast cancer, a major threat to women’s health worldwide, involves growth of cancerous cells within breast tissue. In United States, next to non-melanoma skin cancer, breast cancer remains the most prevalent cancer in women and the major cause of death due to cancer. According to latest data facilitated by the U. S. Cancer Statistics Working Group, in the year 2007 the number of women in U. S. diagnosed with breast cancer was 202,964; and the mortality due to the same was 40,598. Women of all races and of Hispanic origin are most vulnerable to this type of cancer. It is the second major cause of death next to lung cancer in white, black, Asian/Pacific Islander, and American Indian/Alaska Native women and the leading cause among women of Hispanic origin (CDC). The incidences of breast cancer have been reported to rise gradually during the last two decades, but mortality has lowered as a consequence of advanced technology making earlier diagnosis possible and better management of the disease. The disease has been rarely reported in men, and is equally dangerous (Thor and Osunkoya, 425). Breast cancer is one of the earliest known forms of cancer in human beings with a 5000 year old history. Reports of early descriptions of the disease date back to 1600 BC. These reports by Smith Papyrus of Egypt report eight cases of breast cancer followed by the conclusion that they could not be cured. Advances in understanding of human anatomy led to establishment of the association of breast cancer with lymph nodes in the armpits during the seventeenth century. Radical mastectomy or complete removal of both breasts is a painful, debilitating procedure with long term impacts. But this procedure introduced by Dr. William S. Halsted of Baltimore; remained the standard procedure for treatment of breast cancers till 1970s. The recognition of breast cancer as a systemic illness curable through simpler procedures was made available much later (Donegan, 12). To develop an understanding of the risk factors, pathophysiology, and recent advances in the understanding of breast cancer is the aim of the present paper. Breast Anatomy and Breast Cancer Breasts are modified skin glands located between the clavicles and sixth to eighth rib on the chest wall, and develop from the mammary ridge in the embryo. The gland tissue or lobules in the breast are responsible for milk production and are connected by ducts to the nipples. Besides the lobules and the ducts, breast also comprises of fatty, connective and lymphatic tissue. Recent studies provide evidence for the presence of more than 20 lobes or segments comprising of major lactiferous ducts involved in conducting milk to the nipples from the lobules. Each lobule, also known as the terminal portion of the duct system; comprises of multiple ductules that form its glandular acini, and the specialized connective tissue enveloping it. The rest of the breast comprises of stromal connective tissues that are histologically distinct. The terminal duct along with its lobular unit; is termed as terminal duct lobular unit (TDLU), and is usually the points of origin of lung cancer. It has been hypothesized that this area possesses stem cells which are responsible for the tumor formation (Kopans, 7). Epidemiology Environmental factors, lifestyle are being reported as major risk factors for breast cancer compared to genetic factors. The recent reports of rising incidences of disease in first generation daughter of Japanese American women have provided support to these reports. However the most significant risk factor is age. Further age related factors such as age at menarche, at menopause and at the time of first childbirth are also risk factors. Women who undergo first childbirth after 30 years of age are more vulnerable to the disease. Women with a benign breast disease and a family history of breast cancer are also at higher risk for developing the disease. Women are a hundred times more susceptible to disease than men (Vogel, 48). Besides the above mentioned risk factors, certain other factors have been recognized during recent researches; however the results obtained still remain inconclusive. Anthropometry is being studied as a major cause contributing to disease development. Higher values of anthropometric variables such as height, weight, body mass index (BMI) etc render postmenopausal women vulnerable to breast cancer. Association between BMI and breast cancer is also influenced by HRT (hormone replacement theory), the latter responsible for raising the risk. Obesity, especially in women above the age of 75, becomes a major risk factor. Other risk factors for breast cancer include endogenous hormones, alcohol consumption, premenopausal smoking, high breast density etc. The factors that have been reported to be favorable and reduce the risks are breastfeeding, premenopausal anthropometry, postmenopausal smoking, and physical activity (Vogel, 48). Pathology Breast cancer pathogenesis is inadequately understood and the disease itself exhibits diversity with respect to histopathology and molecular bases. However, molecular and genetic studies have provided significant insight in to the pathogenesis of the disease. The three genes identified to be associated with breast and ovarian cancer include BRCA1 (a tumour suppressor gene on chromosome 17), BRCA2 (located on chromosome 13q12) and p53 gene (Thor and Osunkoya, 425). Types of Breast Cancer In situ breast cancer includes cancers restricted to ducts (ductal carcinoma in situ or DCIS), and lobules (lobular carcinoma in situ or LCIS); i.e. the tumor remains within its place of origin. In contrast invasive cancer refers to tumor spread beyond the place of origin, the severity of which is determined by the level of invasiveness (Kopans, 7). Pathology of in situ Breast Cancer Ductal carcinoma in situ (DCIS) forms a heterogenous group of breast tumours that have distinct clinical, morphological, genetic and radiologic characteristics. However this class of breast cancers involves the clonal proliferation of cells exclusively inside the basement membrane bound structures. Incidences of DCIS during mammographic screening programs constitute 20-25% of breast cancer incidences. On the basis of morphologic pathological attributes DCIS has been classified in to a number of groups such as comedo (involving central necrosis), cribiform, microcapillary etc. These architectural features enable identification of extent of disease however, most lesions being of mixed type, this type of classification lacks reproducibility. Recent categorization includes attributes such as nuclear grade and luminal necrosis occurrence. While architectural attributes vary within a particular lesion complicating the classification, nuclear grade remains distinct within specific lesion and facilitate definite demarcation (Pinder, 58). High grade DCIS comprises of pleomorphic cells that are large in size and are characterized by more than one large and prominent nuclei. Size of nuclei compared to normal cells such as epithelial cells provides an important criterion for classification of tumors. These cells frequently undergo mitoses, exhibit solid architecture with comedo type of necrosis and are unpolarized. In contrast in incidences of low grade DCIS, cells are smaller in size and regular with smaller and monotonous nuclei that are not prominent. A further mitosis too is a rare event in these cases with chromatin remaining mostly dispersed. Cells have definite margins and also exhibit polarization. An intermediate grade DCIS is also recognized, when the DCIS cannot be distinctly categorized in either of aforementioned categories. Pathology of Invasive Breast Cancer Invasive breast cancer is the more prevalent of the two major groups of breast cancer and is also known as infiltrating ductal carcinoma and carcinoma of no special type. This group of cancer involves tumors that begin within the milk ducts but if untreated can spread through circulatory system to other organs. A breast with an invasive ductal carcinoma (IDC) appears to have a firm and hard lump with irregular margins with the overlying skin often retracted. A mammography reveals either a lump with smooth margin or with calcifications leading to stellate or speculated appearance. Invasive Breast cancer is also a group of carcinomas comprising of several types such as infiltrating ductal, invasive lobular, ductal lobular, tubular, medullary, papillary, mucinous etc (Li et al., 1046). Figure 1: Histologic subtypes of Invasive Breast Cancer among mammographically screened patients (Sahin, 199) Due to the wide heterogeneity in characteristics of IDC, the diagnosis of specific subtype is based on the exclusion of special types of breast carcinomas rather than on direct diagnosis. At clinical levels several criteria are used to classify the subtypes of IDC including patient age, tumor size and histopathological features such histological grade and lymphovasuclar invasion, axillary lymph node attributes, hormone receptor status and HER2 (human epidermal growth factor receptor 2) factors. Instead of considering these attributes in isolation, categorization is based on combined impacts of these attributes (Schnitt et al., 560). At the microscopic levels IDC exhibits varied clinical features with cells occurring individually; or as diffuse sheets, well formed nests or in form of cords. Cells size and shape also varies but is always large and pleomorphic with abundant and eosinophilic cytoplasm. Gland or tubule may or may not be present and if present may be extensive or focal. Necrotic areas can be clearly identified. Mitoses may also be frequent or rare. The IDC show an immune response to keratins especially low molecular weight keratins such as keratin 7, 8, 18 and 19 (Sahin, 200). Advances in the molecular technology have led to an increasing use of gene expression profiling as the method of choice for assessment of breast cancer. These techniques although still not completely optimized have been able to identify several types of IDC besides the earlier identified hormone receptor positive and hormone receptor negative carcinomas. In the former category are identified molecular subtypes luminal A and luminal B, while in the latter are recognized HER2 and basal like subtypes. These subtypes show great variation in gene expression, clinical characteristics and hence demand different therapeutic protocols and prognosis (table 1) (Schnitt et al., 560). One of the major achievements of gene expression profiling studies is the characterization of basal like breast carcinomas as a distinct molecular subtype. This class though identified three decades before were incompletely understood, but now are known to present as IDC with solid architecture, high grade histological patterns, lack of tubule formation, frequent mitoses, stromal lymphocytic infiltrate and no association with DCIS. At the molecular level they are found to be negative for both estrogen receptor (ER) and progesterone receptor (PR), absence of overexpression of proteins and gene amplification. On the basis of genetic profiling, three biomarkers have been identified for categorization of breast carcinomas: ER, PR and HER2. EGFR and cytokeratin (CK) are also used as biomarkers for breast carcinomas (table 2) (Schnitt et al., 560). Conclusion Despite a history of five thousand years the breast cancer saga is devoid of a happy conclusion. With advanced technology and constant researches, the disease is definitely better understood. In depth knowledge of the cellular and molecular aspects, risk factors and pathophysiology of disease have enabled early detection and better comprehension of the various aspects of the disease. Chemotherapy and mammography have enabled improved disease management. However research continues for better management strategies such as a vaccine that would enable women all over the world to overcome the dread of the disease and deprive its position as the threat it still remains. Works Cited 1. CDC. "Breast Cancer Statistics." November 2010. Centers for disease control and prevention. March 2012 . 2. Donegan, W. L. "History of breast cancer." Winchester, D. J, et al. Breast cancer. Ontario: Walsworth, 2006. 7-12. 3. Kopans, D. B. Breast Imaging. PA, USA: Lippincott Williams and Wilkins, 2007. 4. Li, C. I, D. J Uribe and J. R. Daling. "Clinical characteristics of different histologic types of breast cancer." Br J Cancer (2005): 1046. 5. Pinder, S. E. "Ductal carcinoma in situ (DCIS): pathological features, differential diagnosis, prognostic factors and specimen evaluation." Modern pathology (2010): 58-63. 6. Sahin, A. A. "Pathology of invasive breast cancer." Winchester, D. J, et al. Breast Cancer. Ontario: Walsworth, 2006. 198. 7. Schnitt, S. J. et al. "Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy." Modern pathology (2010): 560-4. 8. Thor, A. D and A. O. Osunkoya. "The breast." Rubin, E and H. M. Reisner. Essentials of Rubin's pathology. Baltimore MD: Lippincott Williams & Wilkins, 2009. 425. 9. Vogel, V. G. "Epidemilogy of breast cancer." Winchester, D. J, et al. Breast cancer. Ontario: Walsworth, 2006. 47-60. Read More