Breast Cancer Pathophysiology Breast Cancer

Advanced Pathophysiology

Breast cancer is the most frequently diagnosed cancer in women worldwide. There are three general determinants associated with the cause of the disease: heredity factors, environmental factors, and hormonal factors. The risk of developing breast cancer increases with age, as 78% of cases are diagnosed in women ages 50 and older. Risk factors are distinguished by their respective etiological influences, such as family history, lifestyle, and exposure to pollutants. The pathophysiology of breast cancer is focused into two cellular models: sporadic clonal evolution and cancer stem cell. The pathological progress of breast cancer stages is understood and is used for diagnostic purposes. Treatment for breast cancer often involves invasive interventions; the future of breast cancer treatment is concentrated within genomic targeted therapies and the identification of cancer stem cell biomarkers as a preventative treatment method.

Breast Cancer

Breast cancer is the most frequently diagnosed cancer for women worldwide (Edwards et al., 2009). In the United States alone, one in eight women will develop breast cancer within their lifetime (Khanna et al., 2011), and cancer is the leading cause of death among women 35-54 years of age (Brody, & Rudel, 2003). The cause of breast cancer has been attributed to family history, environmental, and hormonal factors. The risk of developing breast cancer increases with age, as 78% of cases are diagnosed in women ages 50 and older (Edwards et al., 2009). Numerous risk factors have been identified as influences on the incidence of breast cancer, and speak to the importance for health care practitioners and nurse practitioners to conduct accurate personal and family histories on all women assessed for breast cancer risk. The pathophysiology of breast cancer is multifaceted and is understood within two proposed models of breast cancer cell origin: sporadic clonal evolution and cancer stem cell. Breast cancer advances through stages 0 to IV, in order of increasing invasiveness (Ma et al., 2003). The pathological advancement though the stages is understood and used for diagnoses, however the specific molecular mechanisms of metastasis are not.

Symptoms of breast cancer are usually not clinically apparent until a lump or breast mass has developed, or abnormal tissue is evident following a mammogram. Breast cancer patients benefit from social support and psychological adaptation while engaging in such treatments as chemotherapy, radiation therapy, and surgical interventions. Alternative medicine therapies are also utilized by breast cancer patients. The future of breast cancer treatment is currently focused on genomic targeted therapies and the identification of cancer stem cell biomarkers. Continuing education and awareness of risk factors, and the use of preventative strategies must be continued to reduce breast cancer incidence until new drug therapies are available.

Paper Overview

This paper will evaluate current literature to present the basic pathophysiology of breast cancer, and include discussion on the cause of breast cancer, its associated risk factors, the cancer stages and symptoms, and available treatment options. It will consider the need for social support, psychological effects, and future prospects for breast cancer treatment.

Etiology

The precise etiology of breast cancer is widely unknown. The basic cause of breast cancer is understood as a result of genetic mutations that consequently inflicts abnormal cell growth. There are three general determinants associated with the cause of the mutations: family history and heredity factors, environmental factors, and hormonal factors (Edwards et al., 2009; Gaikwad et al., 2008).

An estimated 5-10% of all breast cancers are the result of an inherited genetic mutation (Edwards et al., 2009). Several mutated genes have been identified as increasing the risk of breast cancer and are attributed to its causal complex. The majority of hereditary breast cancers are caused by mutations in the BRCA1 and BRCA2 genes (Edwards et al., 2009; Brody, & Rudel, 2003). Additional mutations responsible for causing breast cancer have been identified in p53, PTEN, STK11, ATM, and CHEK2 genes (Edwards et al., 2009).

Environmental and lifestyle factors have been studied as causes of many cancers. A patient's body mass index (BMI), alcohol consumption, and diet have been examined as lifestyle factors attributing to breast cancer due to their impact on hormone levels (Brody, & Rudel, 2003). There is also a cause and effect relationship between industrial development and breast cancer, as exposure to pollutants has been observed as a cancer causing agent (Brody, & Rudel, 2003). Few epidemiologic studies have been performed to investigate chemical exposure as a cause for breast cancer, however occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic...

Exposure to estrogens is a risk for breast cancer, and specific oxidative metabolites of estrogens can react with DNA, resulting in endogenous chemical carcinogens (Gaikwad et al., 2008). The damage caused in DNA by these metabolites, in particular, catechol estrogen quinines, results in mutated DNA with the potential to initiate cancer (Gaikwad et al., 2008). Pharmaceutical hormones also affect the cause of breast cancer. The use of estrogen-only and estrogen-progesterone hormone replacement therapy for postmenopausal women increases the incidence of breast cancer (Brody, & Rudel, 2003).
Risk Factors

There are a host of risk factors associated with the development of breast cancer. Identified risk factors reflect the etiological influences associated with breast cancer. Personal history risk factors include a patient's age, reproductive history, prior breast surgery and disease pathology, history of thoracic radiation therapy, prior estrogen and progesterone therapy, weight, alcohol consumption, and breast density (Edwards et al., 2009).

A woman's lifetime breast cancer risk increases with age; 78% of breast cancer cases are diagnosed in women ages 50 and older (Edwards et al., 2009). Reproductive history impacts the risk for breast cancer; menarche before age 12, late onset of menopause after age 55, and first live birth after age 30 have been noted as risk factors (Edwards et al., 2009). High dose radiation in women prior to ages 20 and 30 as part of disease treatment increases breast cancer risks by as much as 40% (Edwards et al., 2009). Numerous health and lifestyle components should be considered when assessing a woman's risk for breast cancer. The consumption of two or more alcoholic beverages a day, lack of exercise, and post-menopausal obesity have been associated with greater risk of developing breast cancer (Edwards et al., 2009). Family history and hereditary breast cancer syndromes also mark significant risk factors. For example, mutations in the BRCA genes are responsible for up to 50%-87% lifetime breast cancer risk (Edwards et al., 2009). A first degree relative, such as mother, sister, or daughter, with breast cancer increases a woman's risk of developing breast cancer by twofold (Edwards et al., 2009). Studies have also shown a link between lower socioeconomic status and incidence of breast cancer (Khanna et al., 2011).

Pathophysiology

The molecular mechanism of breast cancer progression is a linear multi-step development which involves multiple cellular processes. There are two proposed models that account for the cell origin of breast cancer: the sporadic clonal evolution model and the cancer stem cell model (Bombonati, & Sgroi, 2010). The sporadic clonal evolution hypothesis explains that any breast epithelial line can be the target of random mutations, which will result in breast cancer. The cells with advantageous genetic mutations are selected over time to promote tumor growth and progression (Bombonati, & Sgroi, 2010). The cancer stem cell model suggests that only stem and progenitor cells, which constitute a small fraction of cells within the cancer, have the capacity to initiate and maintain tumor progression (Bombonati, & Sgroi, 2010).

The amplification of specific chromosome regions has been identified as frequent events in carcinomas. The amplification of a region on chromosome 8q24 is one of the highest occurring events in ovarian and breast cancers (Guan et al., 2007). Evidence now shows the amplification of the PVT1 transcript within the oncogene MYC also contributes to breast cancer pathophysiology (Guan et al., 2007). In the cancer stem cell model, current research is working towards the identification of specific cell markers that denote the presence of cancer stem cells. Using established cell lines in vitro, CD44 and CD133 cell markers have been identified as indicators of stem cell populations (Charafe-Jauffret et al., 2009).

Stages and Metastasis

The multi-step process of breast cancer development manifests itself as a sequence of pathologically defined stages. The stages of breast cancer are depicted as a number on a scale from 0 to IV; stage 0 describes the noninvasive cancers that have not metastasized and stage IV describes the invasive, metastasized cancers (Ma et al., 2003). Breast cancer initiates as the premalignant stage of atypical ductal hyperplasia, advances into the preinvasive stage of ductal carcinoma in situ, and then progresses and into the lethal stages of invasive ductal carcinoma (Ma et al., 2003). This linear progression model has been employed as a detection method for mammography to identify the stage of breast cancer to diagnose and treat the disease at earlier clinical stages. The precise pathological stages of breast cancer are understood, however the molecular differences among the stages are not. Mesenchymal stem cells have been…