Introduction
Breast cancer affects the breast tissue. There are two forms of this cancer: one type originates from the ducts and is commonly known as ductal carcinoma while that which originates in the lobules is termed as lobular carcinoma. In women, breast cancer accounts for over 22 percent of all cancers (Suter & Marcum, 2007).
The molecular underpinnings of breast cancer are very complex and have different cellular pathways particularly those of cell growth and proliferation. Examples of these pathways include MAPK; TP53; P13K/AKAT/mTOR and RB/E2F (Suter & Marcum, 2007). At the molecular level, these pathways are a representation of molecular mechanisms that are not only composed of, but also regulated by various genes. To be specific, during cell growth and proliferation, genes that are altered include oncogene HER2, ER genes, RAS genes, c-MYC genes, cyclin D1 and E genes, as well as tumor suppressor genes PTEN, TP53, and RB genes (Suter & Marcum, 2007). Others include breast cancer susceptibility genes namely BRCA1 and BRCA2. Breast cancer that is malignant is an exceptionally complex molecular disease that takes center stage when there are alterations in the genes that control cell growth and proliferation. Oncogenes are essential in triggering the cell to undergo cell proliferation. They play a key role in the initiation process and not in later stages.
In addition, mutations in genes that code for estrogen receptors, C-AMP 2 or 4/6, and cyclin D1 and E are also vital in the initiation of breast cancer (Adjei, Dy, and Erlichman, et al., 2004). Human Epithelial Cell (HER) receptor-2 is another important factor. It is involved in the regulation of cell growth and proliferation. Mutations in this gene are risk factors for the development of breast cancer. TP53, for instance, is known as the guardian of the genome. It ensures that the cell’s DNA remains intact. It promotes arrest of the cell cycle, promotes regulated cell death, inhibits angiogenesis and stimulates DNA repair as well as cell proliferation. Mutations in the TP53 mean that products of this gene are abnormal and thus why critical functions like the control of cell death, inhibition of angiogenesis and DNA repair are distorted (Adjei, Dy, and Erlichman, et al., 2004). If the affected cells are in the breast tissue, breast cancer thus develops. In addition, various cells have tumor suppressing genes. They antagonize the functions of oncogenes and as a result they inhibit cell growth and cell proliferation. This leads to unregulated cell growth and the development of breast cancer if the affected cells are in the breast tissue.
Furthermore, the estrogen receptor is also believed to play an important role in the development of breast cancer. To begin with, estrogen is responsible for controlling the mammalian estrous cycle. Estrogen has two distinct receptors: ER alpha and ER beta. Estrogen is a powerful mitogenic hormone. Mutations in the ER alpha gene leads to its over-expression and this is common in the early stages of breast cancer. When estrogen binds ER alpha, a dimer is formed (Adjei, Dy, and Erlichman, et al., 2004). This dimer is then phosphorylated and it induces a conformational change, which exposes the DNA binding domain as well as transcriptional activation domains. This dimer is essential for the phosphorylation of other essential proteins such as the Retino Blastoma (RB), C-AMP 2, and cyclin D1 and E. It has been found that ER and Human Epithelial Cell (HER) receptor-2 share a path during the commencement of breast cancer (Adjei, Dy, and Erlichman, et al., 2004).
Cyclins D1 and E regulate the cell cycle. At the G0 phase, cells are resting. Before they enter the S phase, where DNA replication occurs, cells must pass through the G1 phase. S phase is followed by G2 phase and M phase respectively. During the M phase, cells undergo division. Cyclins bind to Cyclin Dependent Kinases (CDKs). The transition from G1 to phase S of the cell cycle is the most important with respect to the development of cancer. Cyclins D1 and E regulate the transition from G1 phase to the S phase. Growth factors such as EGF and estrogen up-regulate CDK1. CDK1 binds to CDK4/6 and this leads to partial phosphorylation of RB. Consequently, E2F is released, which up-regulates the cyclin E gene. Products of cyclin E then bind to CDK2 and the holoenzyme ensures that RB is completely phosphorylated and inactivated (Alessandro, & Liotta et al., 2004). RB is considered as the master switch that dictates the turning on and off of the cell cycle. In line with this, breast cancer develops when there is deregulation of genes involved in the cell cycle. In fact, CDK1 is overexpressed in individuals with breast cancer (Alessandro, & Liotta et al., 2004).
Research has shown that the dominant form of breast cancer is sporadic in nature in that it stems from oncogenes, which have previously mutated leading to uncontrolled cell proliferation. In addition, other mutations in tumor suppressor genes also contribute to the development and advancement of malignancy. In line with this, it is essential to note that familial or hereditary breast cancer stems from inheritable mutations to susceptible genes as well as other genes (Alessandro, & Liotta et al., 2004). A family member who has inherited mutations of the susceptible genes stands a high chance of developing cancer. Upon exposure to the environmental mutants, the other pair of the genes is altered; a combination of these alterations (genetical and environmental) lead to the commencement of cancer. BCR1 and BCR2 are common in over 82 percent of all familial breast cancer cases (Alessandro, & Liotta et al., 2004). These genes are regarded as high penetrance variance particularly in some ethnic groups;
Molecular evolution
Breast cancer can also be linked to molecular evolution. Molecular evolution is said to have taken place when there are changes in molecules such as DNA, RNA and proteins and this occurs over a long period of time (Sueoka, 1964). Perhaps, mutation is the single most important factor that links molecular evolution and breast cancer (Sueoka, 1964). DNA mutations that are permanent and those which are transmissible are the most dangerous with respect to breast cancer (Sueoka, 1964).
Bioethical Issues and Breast Cancer
There are a number of ethical issues that are associated with breast cancer. They include education of relatives, public and friends, informed consent, patients’ comfort while discussing their conditions with the doctor, (diagnoses and treatments), allocation of scarce resources and access to care.
The progression of breast cancer is still not well understood owing to the complex processes/pathways that are involved. This has derailed the development of therapies which target cellular mechanisms that lead to the development and advancement of breast cancer. Traditional treatment regimes that employ chemotherapy have two main setbacks. First, chemotherapy is nonspecific meaning that it cannot segregate between normal and malignant cells. Unfortunately, this setback causes the second setback which is the accumulation of toxins in the body. In fact the toxic substances are more harmful than the disease itself. Latest chemotherapy drugs have been designed to target malignant cells instead of normal cells.
In summary, this paper has analyzed the genetical and molecular basis of breast cancer. There are two types of breast cancer namely ductal carcinoma, which originates in the ducts and while that which originates in the lobules is termed as lobular carcinoma. The molecular underpinnings of breast cancer are very complex and have different cellular pathways particularly those of cell growth and proliferation. Examples of these pathways include MAPK; TP53; P13K/AKAT/mTOR and RB/E2F. Breast cancer that is malignant is an exceptionally complex molecular disease that takes center stage when there are alterations in the genes that control cell growth and proliferation. Research has shown that the dominant form of breast cancer is sporadic in nature in that it stems from oncogenes, which have previously mutated leading to uncontrolled cell proliferation. Breast cancer can also be linked to molecular evolution. Molecular evolution is said to have taken place when there are changes in molecules such as DNA, RNA and proteins and this occurs over a long period of time. Lastly, there are a various ethical issues that are associated with breast cancer. They include education of relatives, public and friends, informed consent, patients’ comfort while discussing their conditions with the doctor, (diagnoses and treatments), allocation of scarce resources and access to care.
References
Adjei, A. A., Dy, G. K., and Erlichman C, et al. (2004). A phase I trial of ISIS 2503, an antisense inhibitor of H- and clinical outcome. Breast Cancer Res, 6, 188–91.
Alessandro, R., Clair, T., and Liotta, L. A., et al. (2004). The cellular microenvironment. In: Abeloff MD, Armitage JO, Niederhuber JE, et al., editors. Clinical oncology. 3rd ed. Philadelphia, PA: Elsevier Churchill Livingstone.
Sueoka, N. (1964). "On the evolution of informational macromolecules". In In: Bryson, V. and Vogel, H.J. Evolving genes and proteins. Academic Press, New-York. pp. 479–496.
Suter, R., and Marcum, J. (2007). The molecular genetics of breast cancer and targeted therapy. Biologics, 1(3), 1-10. Retrieved on 11 Feb. 2014 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721311/
