Review Article
Breast cancer statistics and markers ABSTRACT Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO 2012. Here, the review is been focused on different breast cancer markers, that is, tissue markers (hormone receptors, human epidermal growth factor‑2, urokinase plasminogen activator, plasminogen activator inhibitor, p53 and cathepsin D), genetic markers (BRAC1 and 2 and gene expression microarray technique, etc.), and serum markers (CA 15.3, BR 27.29, MCA, CA 549, carcinoembryonic antigen, oncoproteins, and cytokeratins) used in present diagnosis, but none of the mentioned markers can diagnose breast cancer at an early stage. There is a disquieting need for the identification of best diagnosing marker, which can be able to diagnose even in early stage of breast carcinogenesis. KEY WORDS: Breast cancer, breast carcinogenesis, markers
INTRODUCTION Cancer has been subsisting from many years, but now it is a major human health problem world‑wide. Over the past 50 years, incidence of cancer all through the world has been increased significantly. Among different types of cancers, breast cancer is a heterogeneous and hormone dependent cancer, representing about 22.9%[1] of total female cancers and it is the second most common type diagnosed in women of developing countries. About one in eight women, one in 1000 men would develop invasive breast cancer over the course of their lifetime.[2] General risk factors of the breast cancer in females are age, infertility, age of first fulltime pregnancy, age of menopause, an inherited mutation in the BRCA1/BRCA2 breast cancer gene and usage of hormones (estrogen and or progestin) in postmenopausal stage. Cancer incidence increases with roughly the fifth power of elapsed age. [3] Low and medium resource countries are arguably harder hit by cancer than high resource countries.[4] Global cancer burden has been estimated that 8.8 million people have died in 2004.[5] The proportion of cancer incidence represented continental were Africa 28.66%, the America 47.50%, Asia 37.5%, Europe 70.08%, and Oceania 57.5%. Global cancer burden could be increased over time with the increase of population. Aging is the major issue for the future cancer burden. Extrapolation of data from past 50 years shows that cancer incidence rate was constantly increasing from year to year. It could be expected 506
that by the year 2030 the incidence rate would be 26.4 million and 17 million cancer deaths could occur in a year.[6] STATISTICS OF BREAST CANCER IN ASIAN REGION Breast cancer is by far the most frequent cancer among women with an estimated 1.7 million new cancer cases diagnosed in 2012 (23% of all cancers), and ranks second overall (11.9% of all cancers), while mortality has increased by 14%. It is now the most common cancer both in developed and developing regions. Breast cancer ranks as the fifth cause of death from cancer overall.[7] Overall risk of breast cancer doubles each decade until the menopause, when the increase slows down or remains stable. However, breast cancer is more common after the menopause. Studies of women who migrate from areas of low risk to areas of high risk assume the rate in the host country within one or two generations. This shows that environmental factors are important in the progression of the disease.[8] According to World Health Organization (WHO) IARC statistics 2012, total breast cancer registries world‑wide was given in Graph 1 and in specific from Asian continent was given in Table 1 and total mortality and registries were represented in Graph 2. According to Globocan (WHO), for the year 2012, India recorded 70,218 deaths due to breast cancer, more than any other country in the world (second: China – 47,984 deaths and third: US – 43,909 deaths).
Mallika Siva Donepudi, Kasturi Kondapalli, Seelam Jeevan Amos, Pavithra Venkanteshan Department of Biotechnology, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India For correspondence: Dr. Kasturi Kondapalli, Department of Biotechnology, Acharya Nagarjuna University, Guntur ‑ 522 510, Andhra Pradesh, India. E‑mail: kasturi. is.kondapalli21@ gmail.com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.137927 PMID: *** Quick Response Code:
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
Donepudi, et al.: Breast cancer statistics and markers
CARCINOGENESIS MECHANISM
Control and American Joint Committee on Cancer and used in most of cancer reports [Table 3].
Genes involved in cell cycle control are important among those subject to the genetic alterations that give rise to cancer.[9,10] The mechanism of cancer development or carcinogenesis, is clearly associated with an increase in cell number, alterations in mechanisms regulating cell proliferation, are only one facet of the mechanisms of cancer. A decreased rate of cell death or apoptosis also contributes to certain types of cancer. Cancer is distinctive from other tumor‑forming processes because of its ability to invade surrounding tissues. Tumor genesis is a multistep process, having five rate limiting steps. They are genetic mutations; that dysregulate the activities of genes, which control cell growth, regulate sensitivity to programmed cell death, and maintain genetic stability. The control of cell division is regulated by a complex interplay of many genes that control the cell cycle, with deoxyribonucleic acid (DNA) replication (S phase) and mitosis as major checkpoints [Figure 1]. Progression through the cell cycle is primarily controlled by cyclins, associated kinases and their inhibitors. Retinoblastoma (rB) and p53 are major suppressor genes involved in the G1/S checkpoint control. Mutation in the tumor suppressor genes such as p53, p16, and p21 lead to the onset of uncontrolled cell proliferation. Inactivation of these negative regulators for a few cell cycles normal checkpoint genes may be activated as oncogenes.[9] In case of breast cancer CCND1 gene encodes cyclin D1 activated as oncogene. Inactivation of this cyclin D1 function results in irregular cell proliferation.[11] GRADE AND STAGE OF TUMORS
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Breast cancer statistics and markers ABSTRACT Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO 2012. Here, the review is been focused on different breast cancer markers, that is, tissue markers (hormone receptors, human epidermal growth factor‑2, urokinase plasminogen activator, plasminogen activator inhibitor, p53 and cathepsin D), genetic markers (BRAC1 and 2 and gene expression microarray technique, etc.), and serum markers (CA 15.3, BR 27.29, MCA, CA 549, carcinoembryonic antigen, oncoproteins, and cytokeratins) used in present diagnosis, but none of the mentioned markers can diagnose breast cancer at an early stage. There is a disquieting need for the identification of best diagnosing marker, which can be able to diagnose even in early stage of breast carcinogenesis. KEY WORDS: Breast cancer, breast carcinogenesis, markers
INTRODUCTION Cancer has been subsisting from many years, but now it is a major human health problem world‑wide. Over the past 50 years, incidence of cancer all through the world has been increased significantly. Among different types of cancers, breast cancer is a heterogeneous and hormone dependent cancer, representing about 22.9%[1] of total female cancers and it is the second most common type diagnosed in women of developing countries. About one in eight women, one in 1000 men would develop invasive breast cancer over the course of their lifetime.[2] General risk factors of the breast cancer in females are age, infertility, age of first fulltime pregnancy, age of menopause, an inherited mutation in the BRCA1/BRCA2 breast cancer gene and usage of hormones (estrogen and or progestin) in postmenopausal stage. Cancer incidence increases with roughly the fifth power of elapsed age. [3] Low and medium resource countries are arguably harder hit by cancer than high resource countries.[4] Global cancer burden has been estimated that 8.8 million people have died in 2004.[5] The proportion of cancer incidence represented continental were Africa 28.66%, the America 47.50%, Asia 37.5%, Europe 70.08%, and Oceania 57.5%. Global cancer burden could be increased over time with the increase of population. Aging is the major issue for the future cancer burden. Extrapolation of data from past 50 years shows that cancer incidence rate was constantly increasing from year to year. It could be expected 506
that by the year 2030 the incidence rate would be 26.4 million and 17 million cancer deaths could occur in a year.[6] STATISTICS OF BREAST CANCER IN ASIAN REGION Breast cancer is by far the most frequent cancer among women with an estimated 1.7 million new cancer cases diagnosed in 2012 (23% of all cancers), and ranks second overall (11.9% of all cancers), while mortality has increased by 14%. It is now the most common cancer both in developed and developing regions. Breast cancer ranks as the fifth cause of death from cancer overall.[7] Overall risk of breast cancer doubles each decade until the menopause, when the increase slows down or remains stable. However, breast cancer is more common after the menopause. Studies of women who migrate from areas of low risk to areas of high risk assume the rate in the host country within one or two generations. This shows that environmental factors are important in the progression of the disease.[8] According to World Health Organization (WHO) IARC statistics 2012, total breast cancer registries world‑wide was given in Graph 1 and in specific from Asian continent was given in Table 1 and total mortality and registries were represented in Graph 2. According to Globocan (WHO), for the year 2012, India recorded 70,218 deaths due to breast cancer, more than any other country in the world (second: China – 47,984 deaths and third: US – 43,909 deaths).
Mallika Siva Donepudi, Kasturi Kondapalli, Seelam Jeevan Amos, Pavithra Venkanteshan Department of Biotechnology, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India For correspondence: Dr. Kasturi Kondapalli, Department of Biotechnology, Acharya Nagarjuna University, Guntur ‑ 522 510, Andhra Pradesh, India. E‑mail: kasturi. is.kondapalli21@ gmail.com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.137927 PMID: *** Quick Response Code:
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
Donepudi, et al.: Breast cancer statistics and markers
CARCINOGENESIS MECHANISM
Control and American Joint Committee on Cancer and used in most of cancer reports [Table 3].
Genes involved in cell cycle control are important among those subject to the genetic alterations that give rise to cancer.[9,10] The mechanism of cancer development or carcinogenesis, is clearly associated with an increase in cell number, alterations in mechanisms regulating cell proliferation, are only one facet of the mechanisms of cancer. A decreased rate of cell death or apoptosis also contributes to certain types of cancer. Cancer is distinctive from other tumor‑forming processes because of its ability to invade surrounding tissues. Tumor genesis is a multistep process, having five rate limiting steps. They are genetic mutations; that dysregulate the activities of genes, which control cell growth, regulate sensitivity to programmed cell death, and maintain genetic stability. The control of cell division is regulated by a complex interplay of many genes that control the cell cycle, with deoxyribonucleic acid (DNA) replication (S phase) and mitosis as major checkpoints [Figure 1]. Progression through the cell cycle is primarily controlled by cyclins, associated kinases and their inhibitors. Retinoblastoma (rB) and p53 are major suppressor genes involved in the G1/S checkpoint control. Mutation in the tumor suppressor genes such as p53, p16, and p21 lead to the onset of uncontrolled cell proliferation. Inactivation of these negative regulators for a few cell cycles normal checkpoint genes may be activated as oncogenes.[9] In case of breast cancer CCND1 gene encodes cyclin D1 activated as oncogene. Inactivation of this cyclin D1 function results in irregular cell proliferation.[11] GRADE AND STAGE OF TUMORS
:25/',1&,'(1&($1'0257$/,7
