Breast cancer is a disease in which malignant (cancer) cells form in the tissues of the breast. Among women in the United States, cancer of the breast is the second most common cancer, and the second most common cause of cancer-related death. Symptoms of breast cancer include a lump or thickening in or near the breast, a change in the size or shape of the breast, nipple discharge or tenderness, and a change in the color or feel of the skin of the breast or nipple. It is important to note that most people diagnosed with breast cancer do not have symptoms and that it is therefore essential to follow recommended screening guidelines.
Breast cancer is commonly known as the second most common cause of cancer-related death in women. Breast cancer is associated with known symptoms and signs while also having a number of identified modifiable and non-modifiable risk factors. It is this paper’s aim to present these risk factors in a succinct and informative manner. With relation to non-modifiable risk factors, this paper will cover genetics, age, sex, race, family history of breast cancer, personal history of breast conditions, high breast tissue density, certain hormone levels, and certain benign breast lumps. This paper will further explore modifiable risk factors such as weight, diet, and alcohol consumption, physical activity, hormone replacement therapy, reproductive history and use of birth control, and environmental exposures.
Definition and Types of Breast Cancer
There are several types of breast cancer, and they are broken into two main categories: “invasive” and “noninvasive” or in situ. Invasive cancers are the most common. They start in the ducts and the lobules and then break through the wall of the duct or lobule and grow in the surrounding tissue. Noninvasive cancers are called “in situ” and are confined to the ducts or lobules and have not invaded the surrounding tissue. These early lesions are further divided into two types: Ductal carcinoma in situ (DCIS): the most common type of noninvasive breast cancer, which originates in the ducts and accounts for about 20% of all new breast cancer cases. It is called “in situ” because it has not invaded the surrounding tissue. At this stage, the cancer has not developed the ability to spread elsewhere in the body. However, if DCIS is not treated, it can transform into an invasive breast cancer.
Breast cancer is a malignant tumor that develops in the breast. It is the most common cancer in women, but it can also rarely occur in men. The breast has a collection of lobules, which are the glands that can produce milk, and ducts that carry milk to the nipples. Cancers can also occur in the fibrous and fatty tissues within the breast. These are called stromal tissues. The most common type of breast cancer is ductal carcinoma, which begins in the cells of the ducts. Breast cancer can also begin in the cells of the lobules and in other tissues of the breast.
Genetic Factors
A number of different strains of mice and several inbred strains of rats show a high incidence of spontaneous mammary tumors. In some mice, the inheritance of mammary tumor susceptibility is autosomal, while in other strains X-linked genes are involved. Both activating oncogenes (or their expression) and inactivating antioncogenes (or their expression) are candidates for such genetic determinants. While major hormonal influences on breast cancer have been studied mostly in estrogen-dependent induced or delayed acting models, genetic factors may be hormone-independent or operate through novel hormonal mechanisms. A major goal of our research is to characterize such novel genetic determinants for breast cancer risk and then to exploit such knowledge for effecting primary prevention in humans. Several such genes do in fact exist, but for several reasons their full number and nature remain obscure.
BRCA1 and BRCA2 Genes
BRCA1 is located on chromosome 17q and is associated with an increased risk for both breast and ovarian cancer. Families in which many members have premenopausal breast cancer or in which both breast and ovarian cancer are diagnosed in the same woman or in a mother and daughter are more likely to carry a BRCA1 mutation. However, not all families meeting these criteria have an identifiable BRCA1 mutation. The lifetime risk for breast cancer in BRCA1 carriers is estimated to be between 50-85% and the risk for ovarian cancer is about 40-60%. Women of Ashkenazi Jewish descent have an increased risk for having a BRCA1 mutation. There are several recurring mutations seen in this ethnic group and testing for these mutations can be performed at a relatively low cost.
The breast cancer susceptibility genes BRCA1 and BRCA2. In recent years, much has been learned about the genetics of hereditary breast cancer. The two major genes associated with breast and ovarian cancer are BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2). When either of these genes is altered and does not function properly, the risk of developing breast cancer is increased. Both of these genes are tumor suppressor genes which, when functioning normally, act to prevent the development of cancer. Mutations in BRCA1 and BRCA2 account for about 2-3% of all breast cancers.
Hormonal Factors
The development of breast cancer is influenced by various hormonal, environmental, and genetic factors. For several decades, research has consistently supported the view that estrogens play a key role in the development of breast cancer. Estrogens are female sex hormones that are produced mainly in the ovaries, where they regulate the menstrual cycle and the development of secondary sexual characteristics. In the breasts, they stimulate the growth of specialized lobular and ductal epithelial cells. Over the years, estrogens have been demonstrated to act via specific receptors: the estrogen receptors (ERα and ERβ), which are members of the steroid hormone receptor family. Upon binding with estrogen, the estrogen receptor complex acts as a transcription factor, leading to gene transcription and changes in the functioning of estrogen target cells.
Estrogens, the female sex hormones, are known to be associated with the development and growth of breast cancers that express estrogen (ER) and progesterone (PR) hormone receptors. The actions of estrogens are mediated through specific estrogen receptors, resulting in changes in gene transcription and the functioning of target cells. Some of the evidence supporting a role for estrogen in breast cancer is: the increased risk of breast cancer following prolonged exposure to estrogen; the increased risk associated with tumors that lose estrogen receptors; the ability of antiestrogen drugs to prevent the development of some breast cancers and limit the growth of others; and the many findings from experimental models. After menopause, when the ovaries stop producing estrogens, it is still possible for breast cancer survivors to produce these hormones from other tissues in the body. The discussion here explains how that happens and discusses the potential implications for breast cancer survivors who produce estrogen after menopause, especially those who have survived ER+ breast cancers.
Estrogen and Progesterone
Women are exposed to estrogen in several ways. The body, for example, produces estrogen. Adipose tissue, or fat, also produces a form of estrogen called estrone. Women who are obese have more estrone and are exposed to more estrogen. A woman’s diet can also contribute. Diets high in animal fats can increase blood levels of estrone. External sources of estrogen also pose a risk. Estrogen replacement therapy (ERT) and hormone replacement therapy (HRT), used to alleviate menopausal symptoms, as well as oral contraceptives (birth control pills), all contain estrogen and can increase the risk of developing breast cancer. Women who have had a combined total of more than five years of exposure to ERT have a risk that is 1.2 to 2.0 times greater than women who have not used it. For women who have taken HRT, the risk is 1.7 to 2.0 times greater. The risk is 1.5 times greater for women who have used oral contraceptives and have a family history of breast cancer.
Estrogen and progesterone are female hormones produced in the ovaries and in smaller amounts in the adrenal glands, which both men and women have. These hormones cause the development of secondary sexual characteristics in women and regulate the menstrual cycle. Breast cells also have receptors for these hormones. This means that when these hormones attach to the receptor, they exert their effect. In the case of breast cells, estrogen promotes cell division, and progesterone prepares the breast for milk production. Some breast cancer cells also have these hormone receptors. In these cells, estrogen and progesterone promote cancer growth. For this reason, estrogen and progesterone are considered risk factors for breast cancer.
Environmental Factors
Comprehensive identification of environmental factors that truly increase breast cancer incidence is hindered by the complexity of the disease, the multistage nature of its development, the long latency period and the lack of cost-effective methods for testing relevant hypotheses. A combination of in silico, in vitro and in vivo approaches is necessary to validate predictions about the potential hazard of certain chemicals. Furthermore, due to individual variability in susceptibility to environmental carcinogens, genetic profiling of breast cancer cases may serve as a valuable tool for the eventual identification of tested genotoxicants.
Breast cancer is generally thought to be precipitated by an interaction of a person’s genetic predisposition with previously identified or as yet unidentified environmental risk factors. Environmental factors suspected of increasing the risk of breast cancer encompass a wide range of exposures including therapeutic and other forms of radiation, chemicals that mimic estrogens (xenoestrogens), industrial pollution as well as lifestyle elements. Of the established environmental risk factors, only ionizing radiation has a strong biologically plausible link with breast cancer. Several studies report alkyl phenolic chemicals, like nonylphenol and its polymer degradation product nonylphenolethoxylate, to adversely affect the estrogen receptor-mediated signaling, thereby increasing the risk of hormonally-induced cancers such as breast cancer. Findings from other studies, however, do not support the link between alkyl phenols and breast cancer promotion.
Radiation Exposure
The risk of breast cancer apparently remains elevated years after radiation exposure. On the basis of these studies, it is apparent that the effect of radiation is to increase the incidence of breast cancer over the entire lifespan, rather than to accelerate the process such that cases that would have occurred later in life are “precipitated” and occur at a younger age. This model is further supported by data from survivors of the atomic bomb blasts in Japan in 1945, who experienced a significant excess risk of breast cancer for the rest of their lives, and by patients treated with radiation for cancer of the cervix, whose risk of developing breast cancer begins to climb 10 years after radiotherapy and continues to increase for the next 30 years. Furthermore, there is no biological “plausibility” to the concept that radiation therapy could induce only a temporary increase in the risk of cancer development. Such a phenomenon might be explained by a scenario in which radiation exposure accelerated the growth of preexisting subclinical, undetectable cancers; however, there is no evidence that such subclinical cancers could exist for decades.
Ionizing radiation is a well-established cause of human breast cancer. The association is strongest for radiation exposure at a young age and for women with a strong family history of breast cancer. The evidence for an association between medical radiation and breast cancer comes from several different sources: therapeutic radiation treatment for a variety of disorders, including noncancerous conditions; epidemiologic studies of atomic bomb survivors; and patients given high-dose radiation for selected types of cancer. Estimates of the relative risk for developing breast cancer associated with radiation exposure vary depending on the nature of the exposure. Women exposed to radiation before age 20 have the greatest risk. Those exposed between ages 20 and 34 have a somewhat lower risk, and those exposed between 35 and 40 have an even lower risk. Not until age 41 and older does radiation no longer increase the risk of developing breast cancer.
Lifestyle Factors
A greater incidence of the disease has been found among women who are overweight, women who have their first child at a late age, women who have no children, women who use oral contraceptives within the previous ten years, and women who have not breastfed their children. The use of hormone replacement therapy and estrogen-progestin therapy further increases a woman’s risk of developing breast cancer.
Hormone Replacement Therapy (HRT): HRT after menopause increases the risk of breast cancer. Combined HRT (estrogen-progestin) increases the risk more than estrogen alone. This higher risk may develop quickly, within 2 years of starting HRT. It is usually advised to use the lowest dose possible for the shortest amount of time needed to relieve symptoms.
Pregnancy and breastfeeding: Both pregnancy and breastfeeding may help reduce the risk of breast cancer, possibly because they reduce a woman’s total number of menstrual cycles. Women who have never been pregnant have a slightly higher risk of breast cancer, similar to the risk in women starting their first menstrual periods at an early age. Similarly, women who have had more menstrual cycles because they started their periods at an early age or went through menopause at a later age are at a slightly higher risk.
Diet and Exercise
For many years, the lay public, and indeed many in the medical and scientific communities, believed that cancer had to be treated with potent new chemicals or drugs. Indeed, despite evidence that other approaches may be effective, relatively little effort has been invested in proving the worth of a broad range of nonpharmacological approaches. It is becoming increasingly evident that several lifestyle factors may influence the prevention of breast cancer. It is important that such associations are adequately researched and described so that they can contribute to the development of cancer prevention strategies that will decrease the incidence of this disease.
Although some of the biggest risk factors for developing breast cancer are simply being a woman and getting older, new research suggests that about 30% of cases can be prevented – remarkably, through simple lifestyle changes. Since cancer is a disease of abnormal genetic expression and many environmental factors influence genetic expression, it is not surprising to find that many factors have been or tend to be associated with an increased risk of breast cancer. It has been estimated that in societies in which women overeat, up to 40% of breast cancer is attributable to dietary excess. Conversely, there is an apparent protective effect of exercise.