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Understanding Breast Cancer Risk
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Submitted By: Healthology, Inc.
Author: Andrew Joe, MD
When estimating the baseline risk of a healthy woman developing breast cancer, the statistic often quoted is 1 out of 8. This often leads to much anxiety, since a 12.5% risk of developing cancer is frighteningly high. However, this is a cumulative risk over one’s lifetime, and half of this risk actually occurs after a woman reaches the age of 65 years.
The following represents a broad overview of factors associated with breast cancer risk, methods to measure breast cancer risk, and options available to women at high risk of developing the disease. Many of these topics are discussed in greater detail in other feature articles in the November Focus and will be discussed throughout the month during Healthology Live audio broadcasts. We encourage you to read on and tune in.
I. Risk Factors
Age is a well-known risk factor for breast cancer with the greatest risk occurring after the age of 55 years. There are many other known endogenous (i.e., related to one’s individual body) and exogenous (i.e., related to lifetime exposures, including toxins, environmental changes, and medicines) risk factors for female breast cancer.
A. Hormonal Factors
The major breast cancer risk factors are "hormonal" and related to a woman’s reproductive history. The greatest risk results following long periods of uninterrupted menstrual or ovulatory cycles. This is because breast tissue, in these situations, is consistently exposed to estrogen. Thus, the early onset of menarche and the late onset of menopause both will increase the number of menstrual cycles in a woman’s lifetime and therefore, increase her risk. Pregnancy will interrupt menses and is therefore protective; a woman who delivers her first child at an early age will have less risk, whereas a woman who has never given birth, is at a much-increased risk of developing breast cancer. Events which delay the onset of, (e.g. extreme physical activity) or eliminate (e.g. oophorectomy, the removal of one’s ovaries) regular menstrual cycles will also decrease cancer risk. Abortion, either miscarriage or voluntary, does not have an effect on cancer risk. It is possible that prolonged breastfeeding may decrease risk in premenopausal women.
Because breast tissue exposure to estrogen increases cancer risk, there has been much interest in evaluating the risk of oral contraceptives and hormone replacement after menopause. The risk of using oral contraceptives was previously controversial, but most would now agree that they do not increase a woman’s risk of developing breast cancer. There is possibly a small increased risk with using hormone replacement. However, there are now well-characterized benefits of hormone replacement therapy for both cardiovascular disease and osteoporosis. Therefore, a woman’s relative risks of breast cancer, cardiovascular disease, and osteoporosis must all be factored when considering hormone replacement therapy during menopause.
B. Genetic Factors
As with other medical conditions, there is a growing belief that the etiology of cancer is, in part, genetic and environmental. Most of the major discoveries supporting the genetic basis of cancer have been in colon cancer and breast cancer.
Over the past decade, two breast cancer susceptibility genes have been discovered and characterized, BRCA-1 and BRCA-2. Certain changes, known as mutations, in either of these genes will increase a woman’s risk of breast cancer and may also increase the risk of other types of cancer, including ovarian, in affected family members. Mutations of these two genes are much more common in the Ashkenazi Jewish population. There are other genes which may confer an increased risk of breast cancer, including p53, and probably multiple other, as-of-yet undiscovered breast cancer susceptibility genes. However, as a group, those with a well-documented genetically inherited predisposition to breast cancer only account for about 5-10% of cases diagnosed in the United States. A personal history of early-onset breast cancer, bilateral breast cancer, or both breast and ovarian cancer, suggests the presence of the mutation in one of these genes. Furthermore, if a woman has more than three relatives with breast or ovarian cancer, it is possible that the mutation may exist within the family members.
In addition to these gene-based, hereditary breast cancer syndromes, there are much more common non-hereditary syndromes in which there is an abnormally high frequency of breast cancer within a family. In these families, there are generally more than one affected first degree relative, and cancer often occurs in women younger than 50 years of age. However, in contrast to hereditary cancer, affected women have a much lower individual risk of developing cancer that rarely exceeds 30%.
C. Environmental and Lifestyle Factors
In addition to the better characterized hormonal and genetic factors that increase the risk of developing breast cancer, there are several known environmental and lifestyle risk factors. The best data exist for alcohol, obesity and physical activity, and high doses of radiation. In contrast, there is no convincing data supporting an increased risk with cigarette smoking.
There is a linear relationship between heavy alcohol consumption and breast cancer incidence: with greater intake, there is a greater risk. This does not appear to hold true for mild-to-moderate levels of consumption, which potentially offers some benefits in fighting cardiovascular disease.
Obese women are generally at an increased risk of developing breast cancer. The theoretical basis for this association is that fatty tissue raises estrogen levels and increases estrogen activity in the setting of obesity. Therefore, factors that promote or decrease obesity are likely to affect breast cancer risk as well. For example, physical activity, both at the workplace and during leisure time, has been shown to decrease the risk of breast cancer. It is likely that dietary fat does not by itself lead to a significantly increased risk of breast cancer, but does increase risk by contributing to obesity.
High levels of radiation exposure will increase the risk of developing breast cancer. Examples of these exposures include atomic bomb radiation and treatment exposures, such as radiation treatment of Hodgkin’s disease. Regarding other common environmental concerns, although some studies have reported a possible relationship, there is no definitive data linking either organochlorine pesticides or electromagnetic fields to an increased risk of breast cancer. Silicone breast implants do not increase the risk of breast cancer. Furthermore, there has been recent concern over the apparently increased incidence of breast cancer in women who reside on Long Island. This incidence does not appear to differ much from other urban and suburban areas of the northeastern United States. An ongoing study is evaluating the actual incidence and risk factors that characterize this region.
D. Benign Breast Disease
Certain benign, or non-cancerous, breast diseases may confer an increased risk of developing breast cancer. These abnormalities are discovered either by physical examination or during mammography. Biopsies of these abnormal areas reveal microscopic findings that are definitely outside the boundaries of normal breast tissue, but are not considered actual "cancers". Some of these microscopic changes, such as "atypical hyperplasia" and "lobular carcinoma-in-situ" will place a woman at an increased cancer risk.
II. Estimating Risk
Breast cancer is the most widely publicized cancer among the general population. Great public awareness of this disease has led to significant advances in its management due to increased funding of research, widespread formation of support groups for victims and survivors, and the assumption of a more active role of patients in their treatment. This heightened public awareness, however, has also led to much anxiety and the concern that breast cancer has reached "epidemic" proportions. Caution must be placed when women and their physicians are discussing potential risk factors for breast cancer in order to avoid overestimation of actual risk. The Gail model, as proposed by Mitchell Gail at the National Cancer Institute, is a clinical tool used to mathematically estimate a woman’s risk of developing breast cancer. This risk estimate is based on known risk factors, including age at menarche, age at the first live birth, the number of first-degree relatives afflicted with breast cancer, and the number of previous benign breast biopsies. However, one has to remember that in approximately half of those women who develop breast cancer, there is no apparent risk factor aside from female sex and age. Furthermore, there is no general consensus on what should be done for a woman who is found to be at an increased risk and there are no established strategies for preventing the development of cancer in high-risk individuals.
III. Options for Women with Increased Risk Estimates
Cancer prevention is a relatively new and growing area in oncology. Unfortunately, once a woman is found to have an increased risk of developing breast cancer, there are no standard recommendations of what she and her physician should do with this information. Options that are available include careful surveillance, prophylactic mastectomy, and enrollment in clinical prevention trials. However, clinical trials demonstrating clinical benefits with any of these modalities are very limited.
Careful surveillance and screening may include breast self-examinations and physician clinical examinations every four-to-six months. Annual mammograms may also be offered to "higher-risk" women at an earlier age, even as early as thirty-five years old. Although logically there is a potential of detecting lesions at an early stage, there is no proven benefit with such surveillance.
Prophylactic bilateral mastectomy is also an option for a woman at increased risk. However, even after such a procedure, the risk of developing breast cancer is not zero. There is often some breast tissue remaining and a continued risk of cancer in this tissue. This is also, of course, an operation associated with tremendous psychological and emotional issues along with significant physical side effects.
A woman who is found to be at an increased risk may also decide to participate in a clinical prevention trial similar to the recently reported Breast Cancer Prevention Trial conducted by the National Surgical Adjuvant Breast and Bowel Project and the National Cancer Institute. This large-scale trial targeted women who were estimated to have a breast cancer risk equivalent to that of a woman in her sixties. Risk estimates were based on the Gail model and included factors such as early menarche, no childbirth or delayed childbirth, affected first-degree relatives, and a history of abnormal breast biopsies. Although tamoxifen was found to significantly decrease the incidence of breast cancer in this population, further confirmatory studies are required to establish the preventive role of this agent.
IV. Conclusion
Breast cancer is clearly a common disease and the most common type of cancer in women. It is also the second most common cause of cancer-related death in women. It is important, therefore, for women to think about their risk of breast cancer and discuss these risks with their physicians. This dialogue is extremely important for a number of reasons. First, most women overestimate their risk of breast cancer and believe that the average lifetime risk of the disease in the United States is far higher than the actual 11%. This overestimation of risk can be associated with tremendous anxiety and stress, which can lead to denial and avoidance of risk-reducing strategies. Second, it is unfortunately the women at above-average risk that frequently don't recognize their risk. With exciting advances made over the past year, both doctors and the general public are continuing to understand more about the management of this disease. Therefore, it has never been more important and more potentially beneficial to acknowledge, understand, and act upon breast cancer risk.
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