Tumor's Negative Role In Breast Cancer

“Cancer” is the name for a group of diseases that start in the body at the cellular level. Even though there are many different kinds of cancer, they all begin with abnormal cell growth with the potential to invade or spread to other parts of the body. These abnormal cells lump together to form a mass of tissue or “malignant tumor”. Malignant means that it can spread to other parts of the body or Metastasize . If the breast is the original location of the cancer growth or malignant tumor, the tumor is called breast cancer. (American Cancer Society, 2014, as cited in cbcf.org)

Over the past decade breast cancer has become one of the most predominant diseases in the United States. Breast cancer starts out as a malignant tumor in the tissues of the breast which is formed from the uncontrolled growth of abnormal breast cells. Breast cancer is the most common cancer in women, but it can also appear in men. (Stephan, 2010)

We have all seen the pink ribbons. They have become a national, if not international symbol for breast cancer support and awareness. Breast cancer knows neither racial boundaries nor age restrictions. Females of all ages and ethnicities can develop breast cancer and it is the leading most common cancer among women. Calling attention to this often fatal disease is important by supporting its victims, families and friends of victims, as well as raising funds for breast cancer research. Though males are not immune from developing a breast cancer, for the purposes of this paper, this paper will be limited to information relating breast cancer in females.

Breast Cancer is made up of glands also known as lubes. In a women breast the small tubes (lobules) carry milk to the nipples (ducts) . Breast cancer begins in the cells that are in the in the ducts. It can also start in other cells of the breast tissues. There is a pathway in the breast called lymph. Lymph causes the cancer to spread throughout the breast. The vessels that carry clear fluid instead of blood connect lymph.

Cancer is listed as the second most common cause of death in western countries; particularly, in adults. Though it has a long antiquity, its prevalence and incidence today is pervasive and the war on cancer has not been promising. Malignant neoplasia is characterized by uncontrolled growth and the ability to metastasize or spread from the original site. Cancer results from mutations that promote cell proliferation and inhibit cell adhesion (metastasis). According to the National Cancer Institute (2016), “Cancer can also spread regionally,

Roughly one in eight women in the United States will develop an invasive breast cancer in their lifetime. In 2016, a projected 246,660 new cases of invasive breast cancer are estimated to be detected, along with an additional 61,000 new cases of non-invasive breast cancer. There are greater than 2.8 million women with a diagnosis of breast cancer in the United States, including women presently being treated and women who have completed treatment. Research developments over the past twenty years have ultimately altered the prognosis of breast cancer care. In recent years, there has been an eruption of life-saving advances against breast cancer. Death rates have declined approximately thirty-six percent, believed to be the product of treatment advancement and earlier detection. This paper is intended for those breast cancer patients who are considering breast-conservation surgery, also known as lumpectomy, followed by intracavitary radiation brachytherapy. Patients must be at least forty years old, with a single primary tumor less than three centimeters, negative surgical margins by at least two millimeters, and be without lymph nodal involvement, to be considered candidates for this form of treatment. Radiation therapy is a highly precise and effective way to extinguish minuscule cancer cells that may have been neglected or undetected during surgery. Radiation is often delivered after breast-conserving surgery to reduce the risk that the cancer will recur in the

Approximately one in five women diagnosed with breast cancer worldwide will have HER-2 positive breast cancer, a notably aggressive form of the disease. In the United States alone XYZ women were diagnosed with HER-2 positive breast cancer in ABC. (CITE) Poor prognosis for patients with breast cancer is dictated by tumor characteristics including high grading (poor differentiation), large tumor size, and lymph node involvement. According to XYZ, HER-2-positive breast cancers tend to be larger, high grade tumors and are more likely to spread to other organs in the

The uncontrollable spread of cancer is the principal event which leads to the death in individuals with cancer and it is the greatest barrier of developing cures for cancer. Metastasis is the progressive spread of malignant cancer cells from the primary tumour to secondary organ in distant sites and this potential is dependent on the specific microenvironment which support them to complete each step of the metastatic process (Poste & Fidler 1980). To understand the molecular basis of metastasis, investigators have now separated the complex and highly selective metastasis process into series of steps to try and solve the problems cause by

Breast cancer is the leading cause of cancer deaths in women worldwide, comprising 14.3% of all female cancer mortalities. It is estimated that 480,000 women died in 2008 due to breast cancer. (WHO, 2008)

Inflammation plays a crucial role in different stages of cancer development and has long been associated with various types of cancer. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance of this pathway in the immune response. The NLRP3 inflammasome has been shown to orchestrate multiple innate and adaptive immune responses. However, little is known about its role in breast cancer. This study was performed to investigate the role of NLRP3 and its activation by calcium oxalate, present in the mammary microcalcifications, in the development and progression of breast cancer. Constitutive expression of NLRP3 was observed in breast cancer tissues evaluated

Research and the resulting data has suggested that angiogenesis plays an essential role in the development of breast cancer, invasion, and metastasis; angiogenesis plays a central role in both local tumor growth and distant metastasis in breast cancer. A blood supply is extremely necessary in order for tumors to grow larger than a few millimeters in size. Tumors can give off chemical signals that stimulate angiogenesis so

Microscopically, inflammatory carcinoma is a type of breast cancer in which dermal lymphatic invasions by tumor is evident. (52)

Evidence for pro-metastatic role of TAMs: Genetic studies in mice have shown decreased rates of tumor growth and metastasis are associated with decreased TAM numbers. Lin and colleagues crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1op) and compared tumor progression in wild-type and mice lacking CSF1. Of note, CSF1 is an important survival factor for macrophages. They observed that the absence of CSF-1 significantly reduced lung metastases. However, transgenic expression of CSF-1 in the mammary epithelium of both Csf1op/Csf1op and wild-type tumor-prone mice led to accelerated disease progression and to a significant increase in lung metastasis, which was associated with an enhanced infiltration of TAMs into the primary tumor. In this mouse model, they also observed that TAMs play a crucial role in the ‘‘angiogenic switch” when hyperplastic lesions develop into early stage mammary carcinomas. Similarly, in another study using transplanted tumors, CSF1 depletion resulted in an impairment of tumor growth accompanied with extensive necrosis and poor vascularization, which could be reversed by treatment of mice with CSF1 (Nowicki). These studies provide strong evidence that TAMs promote malignant tumor progression.

Metastatic Breast Cancer is characterized as a severe stage of the breast cancer that continuously spread to other organs. In order to propose a chemotherapy mechanism to the metastatic breast cancer, Aboody and her group induced human neural stem cell (NSC) in a preclinical nude mouse model to target tumor metastases. They were able to propose a therapeutic implication that may prevent the progression of the metastatic by confirming a significant correlation relationship between NSC tumor with hallmarks of breast cancer, by finding a major cytokine (IL-6) that attracts NSC tropism to breast cancer cells, by determining the specific tumor metastatic sites of NSCs with IL-6 expression, and by designing a NSCs that can secrete an enzyme involved in drug metabolism. (Figure 1,2,5) Both negative and positive result experiment verified that NSCs were selectively migrating and invading tumor and metastases on selected sites of tumor metastases, which are lymph node, lung, femur, and liver in the early stage and brain at a later stage.

Breast cancers mostly invade into adjacent regions and metastasize to lymph nodes and distant organs. To develop novel treatments strategies, it is essential to address factors underlying tumorgenesis, invasion and metastasis. In this study, we identified Bmi-1, S100A4 and claudin-1 as important players in breast cancer progression. The current study illustrated the expression of these markers in primary breast cancer tissues, followed by demonstrating the association between their expressions and clinicopathological features and finally addressed their role in breast cancer prognosis.