Current Advances in Breast Cancer Research: A Molecular Approach

Shankar Suman, Garima Suman, Sanjay Mishra

• Publisher: Bentham Science Publishers
• Year: 2020
• ISBN:
  9789811451447
• Topic: Medicina
• Subtopic: Oncología

Breast cancer is a recognized disease around the world with varying patient outcomes based on the type of breast cancer, access to healthcare and other factors. Survival rates for breast cancer are significantly lower in metastatic cases than localized cases. Early diagnosis and effective treatments for the efficient management of breast cancer are now in demand, as they help to prolong patient life. There have been many breakthrough developments in the molecular biology of breast cancer research in recent times. Advancements in diagnostic techniques (imaging and biomarker detection) for breast cancer have improved the screening of the disease and have improved patient outcomes. Despite these enhancements, the disease is still lethal for patients and the search for a cure requires a complete understanding of the disease.
Current Advances in Breast Cancer Research: A Molecular Approach presents a comprehensive overview of current basic and translational research on the subject. The 14 chapters of the book give emphasis to current knowledge about breast cancer, ongoing challenges, and innovative research findings by different research groups. Readers will find detailed information about breast cancer biology, genetics, clinical diagnostics and treatments. Additional information for advanced readers in life sciences, such as techniques relevant to genomics (including genetic fingerprinting), proteomics, metabolomics and medicine (such as imaging and molecular diagnostics) is also provided. The combination of both basic and advanced information makes this book a useful reference to the student and researcher, alike, seeking an understanding about breast cancer at a molecular level.

Genomic Fingerprint of Molecular Mechanisms of Breast Carcinogenesis

Akanksha Nigam^{1, *}, Shivam Priya²

¹ Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

² Institute for Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel

Abstract

Breast cancer in women is the most frequent cancer with the highest mortality worldwide. The risk factor includes aging, family history, genetic predisposition, and hormone factor. In recent years, many new gene signatures have been identified, which have a profound effect on breast cancer initiation and progression. Extensive research has been done in the past five decades in understanding breast cancer biology through genomics and proteomics. All these comprehensive studies from breast cancer patients elucidate heterogeneity of disease as one of the complex problems in its treatment and management. The outburst of molecular information has led to an understanding of the biological diversity of breast cancer. The involvement of various genes at different steps of cancer progression, such as proliferation, evading apoptosis, migration, immunosuppression, and chemoresistance, have been described in this chapter. With the advent of miRNA and splicing factors, new differential regulators of genes have been identified in breast cancer. The breast cancer therapeutic approach can be accomplished by identifying the oncogene and tumor suppressor genes at an early stage of the disease. Elucidation of novel genes in breast cancer will lead to identifying new molecular pathways that may be targeted for its treatment. For the prognostic and diagnostic treatment of breast cancer it is very important to identify newer genomic fingerprints and to develop novel therapeutic targets against them. Our main goal is to make available inclusive understanding of molecular mechanisms and hallmarks of breast carcinogenesis.

Keywords: BRAC1, Breast Cancer, Chemoresistance, HER2, Metallo-estrogens, mi-RNA, miRNA, Molecular Fingerprinting, TNBC, TME, Treg, Trastuzumab.

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^* Corresponding author Akanksha Nigam: Department of Microbiology and Molecular Genetics, IMRIC, the Hebrew University-Hadassah Medical School, Jerusalem, Israel; E-mail: [email protected]

INTRODUCTION

Breast cancer (BC) in women is the most common cancer and the leading cause of

cancer mortality in women; it accounts for 1,300,000 cases and 450,000 deaths each year worldwide [1]. The survival rates of BC patients hugely vary between high and low-income countries. The survival rate is 80% for high-income countries, which reduces to half, i.e., 40%, in low-income countries [2, 3]. In low-income countries, the early detection and treatment of BC is a difficult task [4]. Whereas, in high-income countries like the USA (1975–2000), a continued effort has resulted in a substantial reduction in breast cancer-related deaths [5]. According to the origin of the tumor, BC can be classified as the ductal and lobular tumor. Ductal tumors, which comprise 80% of the tumor, originate in the breast ductal region, and lobular tumors (10-15%) develop from the lobular region [6]. The breast carcinogenesis involves many sequential steps, starting with hyper-proliferation of duct, immunosuppression, leading to invasiveness, and lastly into metastatic status [7]. In this chapter, we will be focusing on risk factors, oncogene, hormone receptors and various hallmarks of BC (proliferation, chemoresistance, TME, mi-RNA, splicing factor). It will be a piece of consolidated information about various molecular fingerprinting genes involved in the induction of breast carcinogenesis (Fig. 1).

Risk Factors

Normally, there is a balance between negative and positive growth factors in breast tissue, but any imbalance may lead to the development of BC [8]. The following few factors are thought to be related to BC development:

Age

The probability of developing breast cancer increases with the age of women. The lifetime risk for women is very low (1 in 8 women) in the USA. This ratio is even lower (1 in 200 women) for women at an early age (≤39 years), but as the age increases(40-59 years) chances of getting breast cancer also increases (1 in 26 women). This age-related BC incidences further increase in low-income group countries [2, 3]. As women grow older, the chances of having abnormal changes in their cells increase in multi-fold magnitude [1, 3, 4].

Family History

Women with a family history of BC increase the risk for the next generation of women. If a woman is diagnosed with BC at the age of 50 or older, than the chances of her daughter developing BC in the future is relatively high. This comparative risk of BC further increases in daughter, if mother had BC before the age of 50 years [9, 10].

Fig. (1))
Diagrammatic representation of different factors responsible for causing breast cancer.

Genetic Predisposition

In BC, there are several inherited genes linked with a genetic predisposition in patients. It is estimated that 25% of patients have a family history of BC, but only 5-10% of cases show the inheritance to next-generation [11, 12]. Genetic predisposition alleles carry 40-85% of lifetime risk, which mainly includes the mutations in BRCA1, BRCA2, TP53, PTEN, STK11, CDH-1 genes. Most mutations in BRCA1 or BRCA2 genes are involved in a high risk of BC. Some other genes are also moderately involved in the occurrence of breast cancer, which include ataxia-telangiectasia (ATM) mutations [13]. The clinical applications of these mutations are still unidentified.

Hormonal Factors

There are so many hormonal dynamics that are directly associated with BC initiation and progression. Early menarche is one of the high-risk factors in women for developing BC. It has been found that women who had early menarche have a higher risk of developing BC at a later stage of life. The initiation of menstruation cycle at an early ag...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• FOREWORD
• PREFACE
• List of Contributors
• Breast Cancer: A Global Burden
• Current Imaging Techniques in Breast Cancer: An Overview
• An Overview of Genetic, Proteomic and Meta-bolomic Biomarkers in Breast Cancer
• Recent Proteomics Development for Biomarker Detection in Breast Cancer
• Deregulation of Enzymatic Post-Translational Modifications in Breast Cancer
• Genomic Fingerprint of Molecular Mechanisms of Breast Carcinogenesis
• Perspectives of Deregulated Metabolism in Breast Cancer
• Oxidative Stress and Lifestyle-based Changes in Breast Cancer Progression
• Epithelial-Mesenchymal Transition (EMT) in Breast Cancer: An Overview
• miRNA Biology in Breast Cancer Progression
• Calcium Signaling in Breast Cancer: Current Perspective
• Role of Mitochondrial-mediated Pathways in Breast Cancer: An Overview
• Advances of the Current Therapeutic Approach for the Management of Breast Cancer
• Micro and Nano-scale Technologies for Breast Cancer Detection and Destruction