Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best "treatment" of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
Breast cancer is the second leading cause of cancer death in women in the United States, with approximately 200,000 cases diagnosed each year. Progress in the areas of screening and treatment may allow for earlier detection and higher cure rates.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person's environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity or Genetic Factors
Women with a family history (mother, sister, aunt, grandmother or cousin) of breast cancer are at an increased risk for developing the disease. The majority of hereditary breast cancers occur in women with a specific genetic abnormality. This is referred to as the BRCA1 or BRCA2 gene, which are located on chromosomes 17 and 13, respectively. Women with the BRCA1 gene have an 85% risk of developing breast cancer, a 60% risk of developing ovarian cancer by age 70 and an increased risk of colon cancer. Individuals with the BRCA2 gene are also at an increased risk of developing breast and ovarian cancer, although their risk is lower than those with the BRCA1 gene.
Women who have previously had breast cancer are at an increased risk for a recurrence. In addition, women who have previously had ovarian cancer or endometrial cancer have a greater risk for developing breast cancer.
Some clinical research suggests that women with female fraternal (two egg) twins have more than twice the risk of developing postmenopausal breast cancer compared to women who do not have a twin. The risk for women with a male twin was also elevated, though the risk for identical (one egg) twins was no higher than the risk for women without a twin.
In addition to the BRCA1 and BRCA2 genes, breast cancer has also been associated with some other syndromes. The rare Li-Fraumeni syndrome (LFS) can involve premenopausal breast cancer in combination with brain tumors, childhood sarcoma, leukemia and lymphoma, and adrenocortical carcinoma. A mutation in the p53 gene has been identified in over 50% of families with LFS. Women with the Li-Fraumeni gene are very likely to get breast cancer, but because of the rarity of this gene, it is not a major cause of breast cancer and is thought to be responsible for less than 1% of all breast cancer cases. Cowden's syndrome is an inherited skin condition that is associated with a higher risk for developing malignancies such as breast cancer, gastrointestinal malignancies and thyroid disease. Women with Cowden's syndrome have a 25% to 50% risk of developing breast cancer. However, this is also rare and not a major cause of breast cancer.
Environmental or Non-Genetic Factors
Several risk factors have been associated with an increased incidence of breast cancer. These include an early age at first menstrual cycle and a late age at menopause; the risk increases with a higher number of menstrual cycles. Additional risk factors include a late age at the birth of the first child, the use of hormone replacement therapy, the use of oral contraceptives, a high-fat diet and obesity.
Some research indicates that there is a relationship between ovarian hormones and breast cancer. In one study that evaluated the relationship between concentrations of ovarian progesterone and the incidence of breast cancer in several countries, researchers found that high concentrations of ovarian progesterone are strongly associated with an increased risk of breast cancer. Furthermore, increased levels of progesterone were associated with an increased caloric intake, indicating that ovarian function responds to nutritional status.
Smoking is associated with an increased incidence of hormone receptor-negative breast cancer. The results of a study conducted in Sweden indicate that female smokers and ex-smokers who develop breast cancer are twice as likely to develop estrogen receptor-negative breast cancer, which may have a worse prognosis.
HCA: Heterocyclic amines (HCAs) may play a role in the development of breast cancer. Several studies have shown that women with breast cancer consumed more HCAs in their diet, due to a large consumption of well-cooked red meat.
DDT: The pesticide DDT has been shown to increase the growth of breast cancer cells. Both laboratory and wildlife studies suggest a link between DDT and higher estrogen levels. The use of DDT in the United States was banned in 1973 and the level of DDT in Americans' blood is 10 times lower than it was during the 1970s. The subsequent decrease in US breast cancer rates suggests a link between DDT and breast cancer.
Red Dye No. 3: There may be a link between Red Dye No. 3 and breast cancer. In clinical studies, when Red Dye No. 3 is placed in the presence of breast cancer cells, the cells increase. Red Dye No. 3 is present in some processed foods.
Prevention
Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.
However, the situation with breast cancer is more complex than with some other cancers and the cause of most cases of breast cancer remain unknown. The risk factors, listed above, do not account for the majority of cases of breast cancer and we must continue to seek these unknown causes.
Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.
There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit is an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates have the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.
It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.
High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants.
There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer. Although excessive alcohol ingestion and all tobacco use are best avoided, they are not major causes of breast cancer.
The results from a study conducted in several different countries indicate that there is a significant link between the risk of breast cancer and the nutritional status of a population. The study demonstrated that high concentrations of ovarian progesterone are strongly associated with an increased risk of breast cancer and furthermore, that a high caloric intake/nutritional status led to increased levels of ovarian progesterone. Thus, decreasing caloric intake could lead to lower concentrations of ovarian progesterone and consequently result in reducing the risk of breast cancer.
Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer. The association between exercise and breast cancer is not as well defined.
Women who maintain consistently high activity levels throughout their lives have a lower risk of developing breast cancer than their inactive counterparts. The Shanghai Breast Cancer Study evaluated activity levels in 1,459 women with breast cancer and 1,556 age-matched controls. Women who exercised during adolescence and adulthood experienced the most significant reduction in breast cancer risk.
Hormone Replacement: There is no doubt that hormone replacement with estrogens or progestins or both increase the incidence of breast cancer in post-menopausal women. However, this risk has to be weighed against the beneficial effects of hormone replacement. Fortunately, breast cancers developing in women on hormone replacement tend to be slow growing, thus allowing them to be detected early when they are highly curable. Women should consider all of the risks and benefits of hormone replacement, rather than simply evaluating this therapy based on the effects it has on one disease.
Oral Contraceptives: Oral contraceptives are associated with an increased risk of breast cancer and a decreased risk of ovarian cancer. As with hormone replacement therapy, the risks and benefits have to be weighed carefully and all factors considered.
Breastfeeding: Long-term breastfeeding may reduce a woman's risk of developing breast cancer by as much as 50%. In a study conducted in China, researchers found a significant association between the duration of lactation and a reduced breast cancer risk. In this study, women who breastfed a child for more than two years had a 54% reduced risk of developing breast cancer, compared with women who breastfed for 6 months or less. In addition, the results indicated that women who had a lifetime duration of lactation anywhere from 73 to 108 months had a significantly lower risk of developing breast cancer. The risk was further decreased for women who breastfed for 109 or more months of their lives. The researchers concluded that prolonged lactation reduces the risk of breast cancer and found that both the duration of lactation per child and the lifetime duration of lactation were important factors.
Prevention for Women at High Risk
Women with a family history of breast cancer and women who carry the BRCA1 and BRCA2 genes are at an increased risk of developing breast cancer and may opt to take more aggressive preventive measures, such as the use of anti-estrogen therapy, prophylactic (preventive) bilateral mastectomy, and/or prophylactic oopherectomy.
Chemoprevention: Nolvadex® (tamoxifen) is a chemopreventive drug that blocks estrogen from entering the cells. Nolvadex® and other anti-estrogens are commonly used in the treatment of breast cancer, but have also proven successful in the prevention of cancer in women at high risk.
Breast cancers are classified as estrogen-receptor positive or estrogen receptor-negative. Estrogen receptor-positive breast cancer is characterized by the presence of estrogen receptors within the cancer cells. Anti-estrogens block these estrogen receptors, thereby preventing the estrogen-stimulated growth of the breast cancer cells. Some women who are at a high risk for developing breast cancer may opt to use anti-estrogens, such as Nolvadex®, in the hopes of preventing the cancer from occurring.
Research indicates that Nolvadex® is effective against estrogen receptor-positive breast cancer. In addition, researchers from the University of Washington have discovered that Nolvadex® may benefit women who carry the BRCA2 mutation, but may not benefit women who carry the BRCA1 mutation. The researchers worked in collaboration with the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to perform genomic resequencing of DNA from blood samples from the Breast Cancer Prevention Trial (BCPT) that was conducted during the 1990s. The study focused on 288 of 315 women who developed invasive breast cancer during the original trial. With the data, the researchers were able to calculate risk ratios for women who received Nolvadex® versus those for women who received placebo. The results indicated that Nolvadex® reduced the risk of breast cancer by 62% in women with BRCA2 mutations, but had no effect for women with BRCA1 mutations. The researchers acknowledged that this reduced risk was similar to the reduced risk offered by Nolvadex® for estrogen receptor-positive tumors.
Cancer of the uterus is an uncommon complication of anti-estrogen therapy. Since the majority of uterine cancers will be detected at an early stage when they are highly curable, the overall benefit of anti-estrogen treatment in breast cancer patients probably outweighs the risk of uterine cancer. All women who have a uterus and are receiving anti-estrogen therapy should undergo regular gynecologic examinations.
In response to the risks posed by anti-estrogens, another class of anti-estrogens has emerged. These are called selective estrogen receptor modulators (SERM) and they are believed to have positive effects on bones as well as anti-estrogen effects on breast cancer without increasing the risk of uterine cancer.
Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by the FDA for the treatment of osteoporosis in postmenopausal women. The Multiple Outcomes of Raloxifene Evaluation (MORE) study was a double blind, placebo-controlled, randomized clinical trial designed to evaluate the effects of long-term raloxifene therapy for the treatment of osteoporosis in postmenopausal women. An additional secondary end point of the trial was the incidence of breast cancer.
The study involved 7,705 postmenopausal women up to 80 years old with osteoporosis who were randomly assigned to receive either placebo, 60 mg of raloxifene a day or 120 mg of raloxifene a day for four years. The results of this study indicated that raloxifene reduces breast cancer risk in postmenopausal women with osteoporosis regardless of lifetime estrogen exposure, but was especially beneficial to those with high lifetime estrogen exposure.
Bilateral Prophylactic Mastectomy (Preventive removal of both breasts): Women who have a family history of breast cancer and women who carry the BRCA1 and BRCA2 genes may reduce their risk of developing breast cancer by 90% by undergoing bilateral prophylactic mastectomy. Prophylactic mastectomy is a drastic measure that may decrease emotional stress regarding the concern over developing breast cancer; however, it may also increase stress related with self-esteem, sexuality and femininity. Women considering this procedure need to weigh the benefits against the consequences, which include the irreversibility of the procedure, the psychological impact and potential problems with implants and reconstructive surgery. While this procedure can greatly decrease the risk of developing cancer, it is not a guarantee that cancer will not develop.
Prophylactic Oopherectomy (Preventive removal of the ovaries): The BRCA1 and BRCA2 genes increase the risk of both breast and ovarian cancer. Since the ovaries produce estrogen, which is linked to the development of both cancers, some women who are at a high risk for developing either cancer will opt to have the ovaries removed. This is an extreme measure and the decision to undergo such a procedure rests in the hands of the patient. Women considering this approach need to weigh the benefits against the consequences, which include sterility and the potential that they could still develop cancer. In addition, removal of both ovaries prior to menopause can introduce the issue of hormone replacement therapy, which carries its own risks.
Screening and Early Detection
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.
While all women over the age of 40 should undergo routine screening for breast cancer, women who are at a high risk for developing cancer may want to begin this process at an earlier age and with greater frequency. Increasing surveillance can increase the possibility that cancer could be found at an early stage when treatment is most likely to produce a cure.
Annual Physical Exam/Breast Self Exam (BSE): Regular physical examination plays a vital role in the maintenance of health. An annual gynecological examination is an important screening procedure for many types of cancer and includes a physical examination of the breasts. During this procedure, a physician physically examines the breasts to feel for any lumps or irregularities. The physician can also use this procedure as an opportunity to teach an individual how to perform a breast self exam (BSE). Women are encouraged to perform a BSE every month, because with regular examination they have a greater chance of finding a lump early in its development.
Mammography: It is recommended that women over the age of 40 begin having a yearly mammogram. A mammogram is an x-ray image of the breast that can reveal irregularities and help to detect cancer early when it is most treatable. Mammography at 6-month intervals is advised for younger women at high risk of developing breast cancer since they tend to develop more rapidly growing cancers.
Increasing surveillance in women with a family history of breast cancer might increase the possibility that cancer could be found at an early stage when treatment is most likely to produce a cure. In a multi-center study, researchers compared mammography performance among women with a first-degree family history of breast cancer with performance among women of a similar age and no family history. The results indicated that the positive predictive value of mammography screening is higher among women with a family history of breast cancer than among those without a family history. The number of cancer cases per 1,000 mammography exams was 1.3 to 2 times higher among women with a family history of breast cancer than among those with no such history. Furthermore, they found that the rate of breast cancer detection among women with a family history of breast cancer was similar to the rate found among women who were a decade older and had no such history.
Predictive Genetic Testing: The identification of the breast cancer susceptibility genes, BRCA1 and BRCA2, has led to predictive genetic testing for these genes. Since most breast cancers are not the result of known inherited mutations, not all women would benefit from genetic testing. However, women who appear to be at a high risk may benefit from undergoing a test to determine if they do carry the BRCA1 or BRCA2 gene. An accurate genetic test can reveal a genetic mutation, but cannot guarantee that cancer will or will not develop. At this point, genetic tests are used to identify individuals who are at an increased risk of developing cancer, so that these individuals may have the option of taking preventive measures.
Strategies to Improve Screening and Early Detection
The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer.
Several new strategies for the screening of breast cancer have recently emerged. Despite progress in this area, it is still important that women continue to utilize the standard screening procedures in an effort to maintain their health and detect breast cancer early when it is most treatable. However, these new procedures hold promise for earlier and more reliable detection of breast cancer and some women may be interested in participating in clinical trials that will help to determine the effectiveness of these new techniques.
Ductal Lavage: Ductal lavage is a safe and simple procedure that has proven successful in detecting cancerous or pre-cancerous cells in fluid extracted from a woman's milk duct. During the procedure, a small, flexible needle is inserted about a half an inch into the milk duct and a salt-water stream washes cells out of the ducts. These cells are then examined under a microscope to check for any abnormalities.
Because most breast cancers begin the breast milk ducts, ductal lavage can detect cancers that are not yet seen on mammography. The procedure has shown potential in clinical trials and thus far, the results support using this test among high-risk women. More research is needed to determine the feasibility of using ductal lavage as a standard screening procedure. The test will not likely replace mammography, but will instead supplement it.
Fiberoptic Ductoscopy: Fiberoptic ductoscopy (FDS) is a new technique that builds on ductal lavage and allows physicians to directly visualize the inside of a milk duct. During this procedure, a small, flexible tube containing a video camera is inserted into the milk duct, creating a live picture of the inside lining of the duct. This allows the physician to visualize the lining of the milk duct and identify any abnormalities. As in ductal lavage, a salt-water stream washes cells out of the duct for examination under a microscope.
In clinical trials, fiberoptic ductoscopy has proven effective in identifying abnormal cellular masses. This procedure is still being evaluated in clinical trials, but could potentially serve as an additional screening procedure, especially for women who are experiencing nipple discharge.
Imaging Devices: Some new imaging techniques have emerged that can provide an image of the breast and identify existing abnormalities. Digital Thermography is being used to complement mammography and to distinguish benign from malignant lesions. The procedure uses changes in temperature to identify cancerous tissue, which will react differently to thermal changes than normal breast tissue. The procedure has already proven effective in identifying malignant lesions and preventing unnecessary biopsies. Computer-aided Diagnosis (CAD) is a procedure employed to review mammogram results and help find abnormalities originally overlooked by radiologists. This technique uses a laser scanner to transform mammography film into digital data. The computer then looks for microcalcifications and deviations in symmetry and flags suspicious areas. A radiologist can then use both the mammogram and the computer output to make a diagnosis. The CAD system acts as a second opinion to the mammogram.
Tumor Biomarkers: Researchers have begun to explore the role of tumor biomarkers for the early detection of breast cancer. In one study, researchers analyzed nipple aspirate fluids (NAFs) from women with and without breast cancer. The results of the study indicated that the levels of carcinoembryonic antigen (CEA) are significantly higher in nipple fluid from cancerous breasts than tumor-free breasts. However, the CEAs appear to be influenced by some unknown systemic influence, which might diminish the usefulness of the biomarker for early breast cancer detection. At this point, analysis of nipple fluid CEA levels might be used in combination with other methods for the early detection of cancer. Future research will help to define the role of nipple fluid CEA levels in the early detection of breast cancer.
Improvements in Genetics: Although the breast cancer susceptibility genes, BRCA1 and BRCA2, are similar, researchers have found significant differences in the genetic profiles of cancers that result from mutations of these genes. Usually BRCA2 mutations lead to estrogen receptor-positive breast cancer, whereas BRCA1 mutations lead to estrogen receptor-negative breast cancer. These differences indicate inherent differences in the genes.
Researchers from the National Institutes of Health evaluated and compared the genetic profiles from BRCA1 mutations, BRCA2 mutations and sporadic breast cancers. They found that the biological characteristics of the tumors were significantly different depending on which type of genetic mutation caused the tumor. The researchers concluded that an inherited mutation influences the gene-expression profile of the cancer. The results of this study have serious implications for the future treatment of breast cancer because the information could lead to individualized treatment for different types of breast cancer that have historically been treated as the same.
Again, the above-mentioned techniques are new areas of exploration in the screening and early detection of breast cancer. Clinical trials are being utilized to determine the effectiveness of these procedures. While the results look promising and the implications could be exciting, these procedures are not yet the standard. It is imperative that women continue to utilize the existing methods of screening for breast cancer in order to ensure early detection. |
