Breast Cancer Screening/Prevention

Overview

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. 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 (e.g. 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

Being Female: Of the close to 200,000 new diagnoses of breast cancer in the United States each year, 99 percent occur in women.[1] For both women and men, risk of breast cancer increases with age.

Family History: Women with a family history of breast cancer have an increased risk of developing breast cancer themselves. In addition, some families are at particularly high risk of cancer due to hereditary cancer syndromes. These families often have multiple family members with cancer, and are more likely to develop cancer at a young age. In the case of breast and ovarian cancers, inherited mutations in two genes – BRCA1 and BRCA2 – have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Alterations in these genes can be passed down through either the mother’s or the father’s side of the family.

Breast Density: Breast density refers to the extent of glandular and connective tissue in the breast. Breasts with more glandular and connective tissue—and less fat—are denser. Women with higher breast density are at increased risk of developing breast cancer. In addition, dense breasts make it more difficult to detect breast cancer by mammography.[2]

Personal History of Breast Cancer or Benign Breast Disease: It is important to realize the women who have been cured of a primary breast cancer are at increased risk for breast cancer in the opposite breast and that this risk persists for 20 years or more.[3] Women with certain types of benign breast disease (such as atypical hyperplasia) also have an increased risk of developing breast cancer.[4]

Environmental or Non-Genetic Factors

Reproductive Factors: Several reproductive factors have been associated with an increased incidence of breast cancer. These include an early age at first menstrual cycle, a late age at menopause, and a late age at the birth of the first child.

Postmenopausal Hormones: Results from the Women’s Health Initiative suggest that postmenopausal hormone therapy with a combination of estrogen and progestin increases the risk of breast cancer.[5] Furthermore, as use of postmenopausal hormones has declined, breast cancer incidence has also declined;[6] this provides additional support for a link between postmenopausal hormone use and risk of breast cancer.

Alcohol: Moderate alcohol consumption (often defined as two or more drinks per day) has consistently been linked with an increased risk of breast cancer.[7]

Obesity: In premenopausal women, obesity has been linked with a decreased risk of breast cancer, possibly as a result of disrupted menstrual cycles and altered hormone levels. In postmenopausal women, however, obesity has consistently been linked with an increased risk of breast cancer. The link between obesity and postmenopausal breast cancer appears to be strongest among women who have never used postmenopausal hormone therapy,[8] [9] and may be explained by the higher estrogen levels in obese postmenopausal women.  A recent study has shown that weight gain in women during adult life increases the risk of postmenopausal breast cancer.[10]

Radiation: Women who have received radiation to the chest for the treatment of Hodgkin’s lymphoma or other cancers appear to have an increased risk of breast cancer. A study has also shown that women who have received low or high dose radiation to the chest have an increased risk of developing breast cancer.[11] Therapeutic doses of radiation have long been known to increase the risk of developing breast cancer. However, this study suggests that diagnostic procedures, such as periodic chest X-rays, can also increase the risk of developing breast cancer.

DES: Diethylstilbestrol (DES) is a synthetic estrogen that was used frequently in pregnant women between the 1940s and 1960s. The drug was used to reduce the risk of miscarriages, though later studies indicated that it most likely had no effect on miscarriage risk. In 1971 a study reported that girls born to women who had used DES (DES daughters) had a greatly increased risk of developing a certain type of vaginal cancer. More recent research suggests that DES daughters may also have an increased risk of breast cancer.[12]

Lack of Exercise: Many studies have shown that women who exercise more have a lower risk of developing breast cancer than women with little physical activity. One study involving over 100,000 women reported that long-term physical activity lowers the risk of developing breast cancer by one third.[13] A study from Europe found that physical exercise reduced the risk of postmenopausal breast cancer by 20-80%.[14]

Prevention

Although many questions remain about the causes and prevention of breast cancer, research suggests that certain behaviors are likely to reduce risk.

Limit Alcohol Consumption: Regular alcohol consumption has consistently been linked with a modest increase in risk of breast cancer;[15] by limiting alcohol intake women are likely to reduce their risk of breast cancer as well as several other types of cancer.

Achieve or Maintain a Healthy Body Weight: Excess body weight has been linked with an increased risk of breast cancer in postmenopausal women.24 By achieving or maintaining a healthy weight, women can reduce their risk of breast cancer and other common, chronic health conditions.

Engage in Regular Physical Activity: Life-long physical activity is an important component of cancer prevention, and several studies suggest that regular physical activity may decrease the risk of developing breast cancer.[16]

Breastfeed: Long-term breastfeeding has been linked with a modest reduction in risk of breast cancer.[17]

Prevention for Women at High Risk

Women with a strong 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 oophorectomy.

Chemoprevention: Drugs that block the effects of estrogen have been shown to reduce the risk of breast cancer in women at high risk of the disease. Two drugs that have been approved for breast cancer risk reduction in certain groups of women are tamoxifen and Evista® (raloxifene).  Tamoxifen is approved for breast cancer risk reduction in women who are at high risk of the disease (including high-risk premenopausal women). Evista – originally approved for the prevention and treatment of osteoporosis –  is approved for breast cancer risk reduction in postmenopausal women with osteoporosis or postmenopausal women at high risk of breast cancer.

Bilateral Prophylactic Mastectomy (Preventive removal of both breasts): Women at high risk of breast cancer may reduce their risk of developing breast cancer by 90% by undergoing bilateral prophylactic mastectomy.[18] 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 Oophorectomy (Preventive removal of the ovaries): The BRCA1 and BRCA2 genes increase the risk of both breast and ovarian cancer. Removal of the ovaries before cancer develops reduces the risk of ovarian cancer by about 96 percent.[19] Surgery doesn’t completely eliminate risk because some cells remain behind after surgery. Removal of the ovaries also reduces the risk of breast cancer since some breast cancers don’t grow well without the hormones produced by the ovaries. Women with a BRCA1 or BRCA2 alteration who have had their ovaries removed have about half the risk of developing breast cancer as those who have not had their ovaries removed. Adverse effects of prophylactic oophorectomy include the inability to have children and the development of menopausal symptoms such as hot flashes.

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.

Mammography: 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. For women at average risk of breast cancer, the U.S. Preventive Services Tasks Force (USPSTF) recommends screening mammography every two years starting at the age of 50.[20] The American Cancer Society, in contrast, continues to recommend annual mammograms starting at the age of 40.[21] Women who have questions about the screening approach that’s right for them are advised to talk with their doctor. Women at high risk of breast cancer may need to begin screening at a younger age.

Clinical Breast Exam: Regular physical examination plays a vital role in the maintenance of health. An annual gynecological examination is an important screening procedure for several types of cancer and includes a physical examination of the breasts. During this procedure, a healthcare provider physically examines the breasts to feel for any lumps or irregularities.

Magnetic Resonance Imaging (MRI): MRI uses radio waves and a magnet to create detailed images of the inside of the body. The American Cancer Society recommends that women at high risk of breast cancer undergo yearly breast cancer screening with breast MRI in addition to mammography.[22] These recommendations were prompted by several studies of MRI screening of women at high risk of breast cancer. While these studies found that the addition of MRI to mammography increased the frequency of false-positive test results compared to mammography alone, it also produced important improvements in breast cancer detection.

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. For more information about genetic testing, please refer to the section Genetic Testing.

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.

Improved Prediction of Risk: Researchers have long sought a way to quantify a woman’s risk of developing breast cancer. Women who learn that they are at high risk of breast cancer can take steps to reduce their risk, and can also undergo more intensive screening in order to detect the disease early when it is most treatable.

The Gail model is a tool that estimates a woman’s risk of developing breast cancer. The model has been used to identify high-risk women for inclusion in breast cancer prevention studies, and has also been used to counsel individual women about their risk of breast cancer. The model considers traditional breast cancer risk factors such as a woman’s age, family history of breast cancer, reproductive history (age at first menstrual period and age at first birth), and history of breast biopsies.

Genetic tests may eventually build upon the Gail model to improve prediction of breast cancer risk. One such test that is being evaluated is called OncoVue.® OncoVue measures genetic variations in single nucleotide polymorphisms (SNPs), which are small genetic changes within DNA that can indicate disease risk. OncoVue uses the genetic information in combination with the Gail model risk factors to predict breast cancer risk. Research suggests that this approach may be more accurate than the Gail model alone in estimating risk of breast cancer.[23]

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 could 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.

New or Improved Imaging Devices: Some new developments in breast imaging are aimed at decreasing the number of false positive tests detected by mammography which leads to a large number of unnecessary breast biopsies.

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.

References


[1] American Cancer Society. Cancer Facts & Figures 2009. Available at: http://www.cancer.org/docroot/stt/stt_0.asp (Accessed July 14, 2009).

[2] Boyd N, Guo H, Martin L, et al. Mammographic density and the risk and detection of breast cancer. New England Journal of Medicine. 2007; 356:227-236.

[3] Hill-Kayser CE, Harris EER, et al. Twenty-year incidence and patterns of contralateral breast cancer after breast conservation treatment with radiation. International Journal of Radiation Oncology* Biology* Physics 2006;66:1313-1319.

[4] Ghosh K, Pankratz VS, Reynolds CA et al. Benign breast disease and breast cancer risk in young women. Presented at the San Antonio Breast Cancer Symposium. December 13, 2008. Abstract 62.

[5] Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321-33.

[6] Ravdin P, Cronin K, Howlader N, et al. The Decrease in Breast-Cancer Incidence in 2003 in the United States. The New England Journal of Medicine. 2007; 356:1670-1674.

[7] Zhang SM, Lee IM, Manson JE, Cook NR, Willett WC, Buring JE. Alcohol Consumption and Breast Cancer Risk in the Women’s Health Study. American Journal of Epidemiology 2007;165:667-76.

[8] Morimoto LM, White E, Chen Z et al. Obesity, Body Size, and Risk of Postmenopausal Breast Cancer: the Women’s Health Initiative (United States). Cancer Causes and Control. 2002;13:741-751.

[9] Lahmann PH, Hoffmann K, Allen N et al. Body Size and Breast Cancer Risk: Findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). International Journal of Cancer. 2004;111:762-71.

[10] Eliassen AH, Colditz GA, Rosner B, et al. Adult weight change and risk of postmenopausal breast cancer. Journal of the American Medical Association. 2006;296:193-201.

[11] John EM, Phipps AI, Knight JA et al. Medical radiation exposure and breast cancer risk: findings from the Breast Cancer Family Registry. International Journal of Cancer [early online publication]. March 19, 2007.

[12] Palmer JR, Wise LA, Hatch EE et al. Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer. Cancer Epidemiology Biomarkers and Prevention. 2006;15:1509-1514.

[13] Dallal CM, Sullivan-Halley J, Ross RK, et al. Long-term recreational physical activity and risk of invasive and in situ breast cancer. Archives of Internal Medicine 2007;408-415.

[14] Monninkhof EM, Elias, SG, Vlems FA, et al. Physical activity and breast cancer: A systematic review. Epidemiology 2007;18:137-157.

[15] Michels KB, Mohllajee AP, Roset-Bahmanuar E, Beehler EP, Boysich KB. Diet and Breast Cancer: A review of the prospective observational studies. Cancer Supplement. 2007; 109:2712-2749.

[16] Scientific Program Committee. Physical activity across the cancer continuum: report of a workshop. Review of existing knowledge and innovative designs for future research. Cancer. 2002;95:1134-1143.

[17] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breast feeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002; 20:187-195.

[18] Rebbeck TR, Friebel T, Lynch HT et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE study group. J Clin Oncol. 2004;22:1055-1062.

[19] Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616-1622.

[20] U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 2009;151:716-726.

[21] American Cancer Society. American Cancer Society responds to changes to USPSTF mammography guidelines. Available at: http://www.cancer.org/docroot/MED/content/MED_2_1x_American_Cancer_Society_Responds_to_Changes_to_USPSTF_Mammography_Guidelines.asp?sitearea=MED Accessed November 17, 2009.

[22] Saslow D, Boetes C, Burke W et al. American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography. CA—A Cancer Journal for Clinicians. 2007;57:75-89.

[23] Dalessandri KM, Miike R, Wrensch MR, et al. Validation of OncoVue®, a new individualized breast cancer risk estimator in the Marin County, California adolescent risk study. 31st Annual San Antonio Breast Cancer Symposium. December 10-14, 2008. Abstract 502.

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