Breast Cancer: Pathophysiology, Risk Factors, and Treatment

Introduction

Breast cancer is the most frequently diagnosed cancer in 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 aged 35–54 (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, underscoring the importance for healthcare 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 the cancer stem cell model. Breast cancer advances through stages 0 to IV in order of increasing invasiveness (Ma et al., 2003). The pathological advancement through these stages is understood and used for diagnosis; however, the specific molecular mechanisms of metastasis are not yet fully elucidated.

Symptoms of breast cancer are usually not clinically apparent until a lump or breast mass has developed, or abnormal tissue is identified following a mammogram. Breast cancer patients benefit from social support and psychological adaptation while engaging in treatments such as chemotherapy, radiation therapy, and surgical interventions. Complementary and 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, along with the use of preventative strategies, must be sustained to reduce breast cancer incidence until new drug therapies are available.

Etiology

This paper evaluates current literature to present the basic pathophysiology of breast cancer and includes discussion of the cause of breast cancer, its associated risk factors, the cancer stages and symptoms, and available treatment options. It also considers the need for social support, psychological effects, and future prospects for breast cancer treatment.

The precise etiology of breast cancer is widely unknown. The basic cause of breast cancer is understood as resulting from genetic mutations that subsequently trigger abnormal cell growth. There are three general determinants associated with the cause of these mutations: family history and hereditary 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 the 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 contributing 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 aromatic hydrocarbons (Brody & Rudel, 2003).

Risk Factors

Hormonal factors have been identified within the context of the molecular etiology of breast cancer. 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 quinones — 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).

There are numerous risk factors associated with the development of breast cancer. Identified risk factors reflect the etiological influences associated with the disease. 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 also impacts risk: menarche before age 12, late onset of menopause after age 55, and first live birth after age 30 have all 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 risk 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 per day, lack of exercise, and post-menopausal obesity have been associated with a greater risk of developing breast cancer (Edwards et al., 2009). Family history and hereditary breast cancer syndromes also mark significant risk factors. Mutations in the BRCA genes are responsible for up to 50–87% of lifetime breast cancer risk (Edwards et al., 2009). A first-degree relative — such as a mother, sister, or daughter — with breast cancer increases a woman's risk of developing the disease twofold (Edwards et al., 2009). Studies have also shown a link between lower socioeconomic status and the incidence of breast cancer (Khanna et al., 2011).