[Immunohistochemical markers as predictive tools for breast cancer]

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Table of Contents

CHAPTER 1: INTRODUCTION1

BACKGROUND OF THE STUDY1

PROBLEM STATEMENT2

PURPOSE OF THE STUDY3

RATIONALE OF THE STUDY3

SIGNIFICANCE OF THE STUDY5

THEORETICAL FRAMEWORK8

BREAST CANCER8

EPIDEMIOLOGY OF BREAST CANCER9

CLINICAL FEATURE13

MICROSTRUCTURE OF BREAST13

HUMAN PAPILLOMA VIRUS (HPV)15

P5317

IHC18

BIBLIOGRAPHY20

Chapter 1: Introduction

Background of the study

The human papilloma virus, or HPV, is already known to directly cause more than 90 percent of all cases of cervical cancer, and this knowledge has been used to develop several HPV vaccines that can dramatically reduce the risk of developing cervical cancer if given to girls and young women before they are exposed to this sexually transmitted virus(Bougeard al. 2006: 531-533). HPV has recently also been linked to an increasing number of cases of oral cancer in patients without the usual risk factors for this cancer (i.e., smoking and increased alcohol intake). Recently, there has been some research evidence suggesting that human papilloma virus (HPV) may also play a role in the development of at least some cases of breast cancer. However, the data linking breast cancer with chronic HPV infection has been rather contradictory thus far, resulting in a lack of consensus about whether or not HPV actually plays any significant role in breast cancer developmen(Bonafe et al. 2003: 4860-4864)t. Now, a newly published research study in the British Journal of Cancer adds more weight to the theory that this cancer-causing (oncogenic) virus may also lead to the development of at least some cases of breast cancer. The authors of this study used two different and complementary tests to evaluate breast tissue specimens for HPV infection. (Dudgeon et al. 2006: 2928-2936)

First described in 1979, and initially believed to be an oncogene, p53 was the first tumour suppressor gene to be identified. p53 functions to eliminate and inhibit the proliferation of abnormal cells, thereby preventing neoplastic development. Abrogation of the negative growth regulatory functions of p53 occurs in many, perhaps all, human tumours. The p53 signalling pathway is in 'standby' mode under normal cellular conditions. Activation occurs in response to cellular stresses, and several independent pathways of p53 activation have been identified that appear to be dependent on distinct upstream regulatory kinases(Aas 1996: 811-814). These include an ataxia-telangectasia mutated (ATM)/human homologue of Rad53 (Chk2)-dependent pathway activated by DNA double-strand breaks, a second pathway dependent on the alternative product of the INK4 gene, p14ARF (which is activated by expression of oncogenes), and a third pathway whose activity is increased by cytotoxic anti-tumour agents and ultraviolet light, but is independent of ATM, Chk2 and p14ARF. Activation of this pathway may be mediated by other kinases such as the ATM relative ataxia-telangectasia and Rad3-related protein (ATR) (Feng 2006: 2812-2819).

Problem Statement

Breast cancer is the most common cancer in women. Its geographical incidence varies worldwide. Despite current advances in the management of Breast Cancer, the ultimate aetiology behind breast cancer remains unknown, however, there are many studies that have investigated risk factors like mutations, age, environmental, and lifestyle factors, but the relationship between breast carcinogenesis at molecular level remains under investigation (Grollman et ...