Breast Cancer Screening: Q&A
Submitted By: Information, News and Press Releases
Source: National Cancer Institute (www.cancer.gov) Posted: 11/16/2009
Breast Cancer Screening: Q&A
Section 1: Breast Cancer Screening
1. What is a mammogram?
A mammogram is an x-ray of the breast. Mammograms can be used to check for breast cancer in women who have no signs or symptoms of the disease. This type of mammogram is called a screening mammogram. Screening mammograms usually involve taking two x-rays of each breast. Together, these four x-rays deliver an effective radiation dose that is about the same as the average person receives from naturally occurring background radiation during a three month period of time. These mammograms make it possible to detect cancer that cannot be felt. Screening mammograms can find microcalcifications (tiny deposits of calcium) and changes in breast tissue that sometimes indicate the presence of breast cancer.
Mammograms can also be used to check for breast cancer after a lump or other sign or symptom of breast cancer has been found. This type of mammogram is called a diagnostic mammogram. Signs of breast cancer may include pain, skin thickening, nipple discharge, or a change in breast size or shape. A diagnostic mammogram may also be used to further evaluate abnormal findings from a screening mammogram.
The goal of screening for breast cancer is to decrease the chances that a woman will die due to breast cancer. Screening can find cancers early, when they are most treatable. Approaches used over the past several decades to finding breast cancer early include mammography, breast self-examination (women systematically search for lumps in their own breasts), and clinical breast examination (doctors or nurses examine women's breasts for lumps).
2. What does the latest NCI-sponsored research tell us about mammography?
In 2009 NCI sponsored a study to model the benefits and harms associated with specific screening schedules at various ages (for example, one comparison looked at annual vs. every other year mammography screening at various ages). To translate the available evidence into health outcomes associated with specific screening programs, computer models made assumptions related to the progression of disease (for example, whether no disease would develop, slowly progressing disease would develop or rapidly progressing disease would occur). For this evaluation, there were six independently developed models, each including unique assumptions but estimating the same outcomes. The independent nature of the models means that the comparative analyses of results were enriched because there was consistency seen across the models.
There were very similar results across the six models studied, with a median reduction in breast cancer mortality of 16.5 percent for women ages 50 to 69 who were screened every other year. Nearly equivalent results were found when looking at a wider age group of 40 to 69. These models have been used to inform decision making by various organizations that are tasked with developing screening recommendations.
[Reference: "Effects of Mammography Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and Harms," J.S. Mandelblatt, K.A. Cronin, S. Bailey, D.A. Berry, H.J. de Koning, G. Draisma, H. Huang, S.J. Lee, M. Munsell, S.K. Plevritis, P. Ravdin, C.B. Schechter, B. Sigal, M.A. Stoto, N.K. Stout, N.T. van Ravesteyn, J. Venier, M. Zelen, and E.J. Feuer, for the Breast Cancer Working Group of the Cancer Intervention and Surveillance Modeling Network (CISNET). Nov. 17, 2009. Annals of Internal Medicine. Vol. 15, No. 10, pp 738-747].
3. What is the best method of detecting breast cancer?
There is no simple answer to this question because it depends on factors such as age and breast density. Standard screen-film mammography that takes a picture with x-rays and uses film is the most widely available technique, and it has been shown to reduce mortality when used regularly in women ages 40 to 74. Digital mammography is becoming more widely available, and it may find cancer more effectively in women with dense breast tissue. Screen-film mammography finds cancer better in women with low density breast tissue. On average, younger women are more likely to have dense breast tissue but once a woman has a screen-film mammogram she can ask her radiologist about her breast density, and she can talk with her health care provide to develop a plan that is best for her.
As with any screening test, screening mammograms have limitations. For example, some cancers cannot be detected by screening mammograms.
Checking one's own breasts for lumps or other unusual changes is called a breast self-exam. Breast self-exams cannot replace regular screening mammograms. In clinical trials, systematically teaching breast self-exams did not reduce the number of deaths from breast cancer, but that does not mean that women should not examine their breasts or report symptoms. If a woman chooses to do breast self-exams, it is important to remember that breast changes can occur because of pregnancy, aging, menopause, taking birth control pills or other hormones, and during menstrual cycles. It is normal for breasts to feel a little lumpy and uneven. It is also common for breasts to be swollen and tender right before or during a menstrual period. If a woman notices any unusual changes in her breasts, she should contact her health care provider.
A physical exam of the breasts by a trained medical professional is called a clinical breast exam. Some evidence suggests that clinical breast exams may help reduce the number of deaths from breast cancer, but this evidence is not as strong as the evidence for mammography.
4. What are some of the limitations or harms of screening mammograms?
· Finding cancer does not always mean saving lives-- Even though mammograms can detect breast changes that cannot be felt, finding these changes does not always mean a woman benefits. Some changes may represent conditions that will reverse to normal breast tissue, and some will not affect a woman's life, even if they are cancer. For some women it may be more important to focus on treating other conditions, improving their physical activity, and eating well than it is to get screened.
· False negatives--False negatives occur when mammograms appear normal even though breast cancer is present. Overall, screening mammograms miss up to 15 percent to 25 percent of breast cancers that are present at the time of screening. False negatives occur more often in younger women than in older women because the dense breasts of younger women make breast cancers more difficult to detect in mammograms. As women age, their breasts usually become more fatty (therefore, less dense), and breast cancers become easier to detect with screening mammograms.
· False positives--False positives occur when radiologists decide mammograms are abnormal but no cancer is actually present. Abnormal mammograms should be followed up with additional testing (a diagnostic mammogram, ultrasound, and/or biopsy) to determine if further investigation is necessary. False positives are more common in younger women, women who have had previous breast biopsies, women with a family history of breast cancer, and women who are taking estrogen (for example, hormone replacement therapy).
· Radiation exposure-- Mammograms (as well as dental x-rays and other routine x-rays) use very small doses of radiation. The risk of any harm is very slight, but benefits often outweigh the risks. Repeated x-rays, however, could cause harm. Women should talk with their health care provider about the need for each x-ray. In addition, they should always let their health care provider, and the technician taking the x-ray, know if there is any possibility that they are pregnant.
· Over-diagnosis-- Mammography can detect cancers that otherwise would never have caused symptoms in a woman's lifetime, and thus lead to unnecessary treatment.
5. Why are mammograms not routinely recommended for women younger than age 40?
Mammograms are not routinely recommended for women younger than age 40 because the incidence of breast cancer is low in younger women. Negative effects of screening include persistent anxiety, unnecessary biopsies, and in some cases, unnecessary treatment. Investigators have estimated that 20 to 50 percent of women will have a positive mammogram after 10 years. This proportion would grow if the screening period were extended to include younger women.
6. What is the Breast Imaging Reporting and Database System (BI-RADS®)?
The American College of Radiology (ACR) has established a uniform way for radiologists to describe mammogram findings. The system, called BI-RADS, includes seven standardized categories, or levels. Each BI-RADS category has a follow-up plan associated with it to help radiologists and other physicians appropriately manage a patient's care.
Additional information about BI-RADS is available at the ACR Web site at http://www.acr.org or by calling the ACR at 1-800-ACR-LINE (1-800-227-5463).
7. What happens if a mammogram leads to the detection of ductal carcinoma in situ (DCIS)?
Over the past 30 years, improvements in mammography have made it possible to detect a wide range of breast tissue abnormalities, including DCIS. DCIS is a condition in which abnormal cells are confined to the milk ducts of the breast. The cells have not invaded the surrounding breast tissue. DCIS usually does not cause a lump, so it cannot be detected during a clinical breast exam or BSE. However, mammography is able to detect 80 percent of DCIS cases. Some of these cases will eventually develop into invasive breast cancer.
It is not possible to predict which cases of DCIS will progress to invasive cancer. Therefore, DCIS usually is removed surgically. In the past, DCIS was often treated with a mastectomy, but breast-conserving therapy (breast-sparing surgery plus radiation therapy) is now standard practice for many women with DCIS. Tamoxifen, a drug shown to prevent recurrence of breast cancer, may also be used. Women who have been diagnosed with DCIS should talk with their health care provider to make an informed decision about treatment.
8. What is the cost of a mammogram and cost of subsequent treatment if breast cancer is diagnosed?
The cost of screening mammograms varies by state and by facility, and can depend on insurance coverage. However, most states have laws requiring health insurance companies to reimburse all or part of the cost of screening mammograms. Women are encouraged to contact their mammogram facility or their health insurance company for information about cost and coverage.
9. How can women who are low-income or uninsured obtain a screening mammogram?
Some state and local health programs, as well as employers, provide mammograms free or at low cost. For example, the Centers for Disease Control and Prevention (CDC) coordinates the National Breast and Cervical Cancer Early Detection Program. This program provides screening services and mammograms to low-income, uninsured women throughout the United States and in several U.S. territories. Contact information for local programs is available on the CDC's Web site at http://apps.nccd.cdc.gov/cancercontacts/nbccedp/contacts.asp or by calling the CDC at 1-800-CDC-INFO (1-800-232-4636).
Information about low-cost or free mammography screening programs is also available through NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). Women can check with their local hospital, health department, women's center, or other community groups to find out how to access low-cost or free mammograms.
10. Where can women get high-quality mammograms?
Women can get high-quality mammograms in breast clinics, hospital radiology departments, mobile vans, private radiology offices, and doctors' offices.
The Mammography Quality Standards Act (MQSA) is a Federal law designed to ensure that mammograms are safe and reliable. Through the MQSA, all mammography facilities in the United States must meet stringent quality standards, be accredited by the Food and Drug Administration (FDA), and be inspected annually. The FDA ensures that mammography facilities across the country meet MQSA standards. These standards apply to the following people at the mammography facility:
· The technologist who takes the mammogram.
· The radiologist who interprets the mammogram.
· The medical physicist who tests the mammography equipment.
Women can ask their doctors or staff at the mammography facility about FDA certification before making an appointment. All mammography facilities are required to display their FDA certificate. Women should look for the MQSA certificate at the mammography facility and check its expiration date. MQSA regulations also require mammography facilities to give patients an easy-to-read report on the results of their mammogram.
Information about local FDA-certified mammography facilities is available through the NCI at 1-800-4-CANCER (1-800-422-6237). Also, a list of these facilities is on the FDA's Web site at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMQSA/mqsa.cfm
11. Should women with breast implants have screening mammograms?
Women with breast implants should continue to have mammograms. (A woman who had an implant following breast cancer surgery should ask her doctor whether a mammogram of the reconstructed breast is necessary.) It is important to inform the mammography facility about breast implants when scheduling a mammogram. The technician and radiologist must be experienced in x-raying patients with breast implants. Implants can hide some breast tissue, making it more difficult for the radiologist to detect an abnormality on the mammogram. If the technician performing the procedure is aware a woman has breast implants, steps can be taken to make sure that as much breast tissue as possible can be seen on the mammogram.
12. What other technologies are being developed for breast cancer screening?
NCI continues to fund research aimed at reducing the already low radiation dose of mammography; enhancing mammogram image quality; developing statistical techniques for computer-assisted interpretation of images; enabling long-distance, electronic image transmission technology (telemammography/teleradiology) for clinical consultations; and improving image-guided techniques to assist with breast biopsies. (A breast biopsy is the removal of cells or tissues to look at under a microscope to check for signs of disease). NCI also supports research on technologies that do not use x-rays, such as magnetic resonance imaging (MRI) and ultrasound to detect breast cancer. The following describes the latest imaging techniques that are in use or being studied, not all of which are being investigated for the screening of breast cancer in average risk women:
Ultrasound, also called sonography, is an imaging technique in which high-frequency sound waves that cannot be heard by humans are bounced off tissues and internal organs. Their echoes produce a picture called a sonogram. Ultrasound imaging of the breast is used to distinguish between solid tumors and fluid-filled cysts. Ultrasound can also be used to evaluate lumps that are hard to see on a mammogram. Sometimes, ultrasound is used as part of other diagnostic procedures, such as fine needle aspiration (also called needle biopsy). Fine needle aspiration is the removal of tissue or fluid with a needle for examination under a microscope to check for signs of disease.
During an ultrasound examination, the clinician spreads a thin coating of lubricating jelly over the area to be imaged to improve conduction of the sound waves. A hand-held device, called a transducer, directs the sound waves through the skin toward specific tissues. As the sound waves are reflected back from the tissues within the breast, the patterns formed by the waves create a two-dimensional image of the breast on a computer.
Ultrasound is not used for routine breast cancer screening because it does not consistently detect certain early signs of cancer such as microcalcifications (tiny deposits of calcium in the breast that cannot be felt but can be seen on a conventional mammogram and may indicate cancer is present) and because it has shown to have a high rate of false positives. A cluster of microcalcifications may indicate that cancer is present.
· Digital Mammography
Digital mammography is a technique for recording x-ray images in computer code instead of on x-ray film. The images are displayed on a computer monitor and can be enhanced (lightened or darkened) before they are printed on film. Images can also be manipulated; the radiologist (a doctor who specializes in creating and interpreting pictures of areas inside the body) can magnify or zoom in on an area. From the patient's perspective, the procedure for a mammogram with a digital system is the same as for conventional mammography.
Digital mammography may have some advantages over conventional mammography. The images can be stored and retrieved electronically, which makes long-distance consultations with other mammography specialists easier. Because the images can be adjusted by the radiologist, subtle differences between tissues may be more easily seen. Digital mammography may reduce the number of follow-up procedures. Digital mammography has been shown to have advantages in women with dense breast tissue, but it is less effective in women with fatty breasts. Overall, digital mammography and conventional mammography are equally effective in finding cancer among women ages 50 and older. Approximately 40 to 50 percent of mammograms nationwide are now done with digital mammography.
· Computer-Aided Detection
Computer-aided detection (CAD) involves the use of computers to bring suspicious areas on a mammogram to the radiologist's attention. It is used after the radiologist has done the initial review of the mammogram.
In 1998 the FDA approved a breast imaging device that uses CAD technology. Other such devices have been developed and are used in clinical practice. The devices identify suspicious areas and highlight them for the radiologist to review. CAD technology may improve the accuracy of screening mammography. The incorporation of CAD technology to digital mammography is under evaluation.
In magnetic resonance imaging (MRI), a magnet linked to a computer creates detailed pictures of areas inside the body without the use of radiation. Each MRI produces hundreds of images of the breast from side-to-side, top-to-bottom, and front-to-back. The images are then interpreted by a radiologist.
During an MRI of the breast, the patient lies on her stomach on the scanning table. The breast hangs into a depression or hollow in the table, which contains coils that detect the magnetic signal. The table is moved into a tube-like machine that contains the magnet. After an initial series of images has been taken, the patient may be given a contrast agent intravenously (by injection into a vein). The contrast agent is not radioactive; it is sometimes used to improve the visibility of a tumor. Additional images are then taken. The entire imaging session times can vary but typically takes approximately 30 minutes.
Breast MRI, a relatively new technology, is not used for routine breast cancer screening. MRI can be recommended in high-risk women because of its proven ability to detect breast cancer that is not visible on mammography. Limitations of MRI include, as with all screening tests, a risk of false positives requiring additional imaging or possibly biopsy. Like ultrasound, MRI cannot detect microcalcifications, although it can detect DCIS that is not evident on mammography.
· PET Scan
A positron emission tomography (PET) scan creates computerized images of chemical changes that take place in tissue. For certain types of PET scans, the patient is given an injection of a substance that consists of a combination of a sugar and a small amount of radioactive material. The radioactive sugar can help in locating a tumor, because cancer cells can take up or absorb sugar faster than other tissues in the body.
After receiving the radioactive drug, the patient lies still for about 45 minutes while the drug circulates throughout the body. If a tumor is present, the radioactive sugar will accumulate in the tumor. The patient then lies on a table that gradually moves through the PET scanner six to seven times during a 45-minute period. The PET scanner is used to detect the radiation. A computer translates this information into images that are interpreted by a radiologist.
PET scans are more accurate in detecting larger and more aggressive tumors than they are in locating tumors that are smaller than eight millimeters and/or less aggressive. PET scans may be helpful in evaluating and staging recurrent disease (cancer that has come back). It is important to distinguish between PET exams of the entire body (used to assess possible disease outside of the breast, such as cancer that has spread to the lymph nodes, liver, lungs, bones or brain) and PET exams under research investigation, which only include the breast and do not provide information from the entire body. These exams, Positron Emission Mammography (PEM), are under research investigation at this time and are not recommended as part of clinical care.
· Image-Guided Breast Biopsy Techniques
Imaging techniques play an important role in helping doctors perform breast biopsies, especially of abnormal areas that cannot be felt but can be seen on a conventional mammogram or with ultrasound. One type of needle biopsy, the stereotactic-guided biopsy, involves imaging the precise location of the abnormal area in three dimensions using conventional mammography. (Stereotactic refers to the use of a computer and scanning devices to create three-dimensional images.) A needle is then inserted into the breast and a tissue sample is obtained. Additional samples can be obtained by moving the needle within the abnormal area. Needle biopsy can also be performed with ultrasound guidance and with MRI guidance. A variety of needle types can be used, from very small needles (fine needle aspiration, or FNA) to larger needles or a needle biopsy device that uses vacuum assistance to sample tissue.
Section 2: Breast Cancer Risk
13. What are the factors that place a woman at increased risk of breast cancer?
The risk of breast cancer increases gradually as a woman gets older. However, the risk of developing breast cancer is not the same for all women. Research has shown that the following factors increase a woman's chance of developing this disease:
· Personal history of breast cancer--Women who have had breast cancer are more likely to develop a second breast cancer.
· Family history--A woman's chance of developing breast cancer increases if her mother, sister, and/or daughter have been diagnosed with the disease, especially if they were diagnosed before age 50. Having a close male blood relative with breast cancer also increases a woman's risk of developing the disease.
· Certain breast changes found on biopsy--Looking at breast tissue under a microscope allows doctors to determine whether cancer or another type of breast change is present. Most breast changes are not cancer, but some may increase the risk of developing breast cancer. Changes associated with an increased risk of breast cancer include:
· atypical hyperplasia (a noncancerous condition in which cells have abnormal features and are increased in number)
· lobular carcinoma in situ (LCIS) (abnormal cells are found in the lobules of the breast)
· ductal carcinoma in situ (DCIS) (abnormal cells are found in the lining of breast ducts). · · · Because some cases of DCIS will eventually develop into invasive breast cancer, this type of change is actively treated. A Sept. 2009 consensus conference sponsored by NCI determined that instead of treating all women diagnosed with DCIS, researchers need to determine which individuals are likely to develop invasive breast cancer and which will not.
Women with atypical hyperplasia and LCIS are usually monitored carefully and not actively treated. In addition, women who have had two or more breast biopsies for other noncancerous conditions also have an increased risk of developing breast cancer. This increased risk is due to the conditions that led to the biopsies and not to the biopsy procedure itself.
· Genetic alterations (changes)--Changes in certain genes (for example, BRCA1, BRCA2, and others) increase the risk of breast cancer. These changes are uncommon; they are estimated to account for no more than 10 percent of all breast cancers.
· Radiation therapy--Women who had radiation therapy to the chest (including the breasts) before age 30 have an increased risk of developing breast cancer throughout their lives. This includes women treated for Hodgkin lymphoma. Studies show that the younger a woman was when she received her treatment, the higher her risk of developing breast cancer later in life.
The following factors can influence risk, but not as strongly as those factors just listed:
· Reproductive and menstrual history--Women who began having menstrual periods before age 12 or went through menopause after age 55 are at increased risk of developing breast cancer. Women who have their first child after age 30 or who never have a child are also at increased risk of developing breast cancer. Women who have a surgical menopause involving removal of both ovaries at a young age have a substantially reduced risk of breast cancer.
· Long-term use of menopausal hormone therapy--Women who use menopausal hormone therapy, especially combination estrogen-progestin, for more than five years have an increased chance of developing breast cancer.
· Breast density--Breast density refers to the relative amounts of different tissue in the breast as seen on a mammogram. Dense breasts have more glandular (milk-producing) and connective tissue than fatty tissue. Low-density breasts have a greater proportion of fatty tissue. Younger women usually have denser breasts than older women. As a woman ages, the amount of glandular tissue normally decreases and the amount of fatty tissue increases. Because breast cancers tend to develop in the dense tissue of the breast, older women whose mammograms show more dense tissue have a higher risk of developing breast cancer. Abnormalities in dense breasts can be more difficult to detect on a mammogram.
· DES (diethylstilbestrol) - The drug DES was given to some pregnant women in the United States between 1940 and 1971. (It is no longer given to pregnant women.) The risk of breast cancer among daughters of the women who took DES is elevated, primarily for those daughters now over the age of 40.
· Body weight--Studies have found that the chance of getting breast cancer after menopause is higher in women who are overweight or obese.
Physical activity level--Women who are physically inactive throughout life may have an increased risk of breast cancer. Being active may help reduce risk by preventing weight gain and obesity.
· Alcohol--Studies indicate that the more alcohol a woman drinks, the greater her risk of breast cancer.
14. What about women who are at very higher risk of breast cancer, such as those with known genetic mutations?
High-risk women would include carriers of known genetic mutations, such as BRCA1 and BRCA2, and women who have undergone radiation to the chest as well as women with multiple family members with breast cancer in their paternal or maternal families. Such women should consult their health care providers about the best personalized screening recommendations.
15. Are African American and other minority women at higher risk of breast cancer?
Overall, African American women develop fewer breast cancers than white women but the death rate due to breast cancer for African American women is higher than that for white women. There is no evidence that mammography can find cancer any better or worse in African Americans, compared to whites, but there is evidence that breast cancer mortality is higher among African Americans. NCI is sponsoring research to model the benefits and risks of screening in African American women and other ethnic and racial minorities.
More specifically, rates of estrogen-receptor negative (those cancers that usually do not grow or spread in the presence of increased estrogen levels) breast cancer for all age groups are higher among some African American populations than among whites. There is no evidence that mammography can accurately distinguish estrogen-receptor negative from estrogen-receptor positive breast cancer. There also are studies which show that a more aggressive subtype of breast cancer is more prevalent among African American and Latina women. NCI is sponsoring studies to evaluate the development, natural history, risk factors and prevention of these subtypes. This information will help to inform the design of future screening studies.
African-American, Hispanic, Asian and other minority women should discuss their screening plan with their health care providers.
16. What is the latest research into risk of breast cancer?
Starting in 2003, the National Institute of Environmental Health Sciences and NCI, both components of the National Institutes of Health, funded four Breast Cancer and the Environment Research Program (BCERPs) centers to study environmental exposures that may predispose a woman to breast cancer throughout her life.
The centers worked collaboratively on two projects: a biology study, "Environmental Effects on the Molecular Architecture and Function of the Mammary Gland across the Life span," and a population study in a group of over one thousand girls, "Environmental and Genetic Determinants of Puberty."
The study of girls helped detect more than 50 environmental agents and their metabolites (including substances known as phenols, phthalates, persistent pesticides, flame retardants and perfluorinated compounds) that could be carcinogens. Many of these substances had not been previously reported in children.
Other, more basic scientific studies led to the discovery of GATA-3 as the master gene for mammary gland development. Related work indicates that the activity of this gene may be a sensitive predictor of tumor predisposition.
17. What can women do to lower their risk of breast cancer?
Exercise, weight control, and moderation in alcohol consumption all have been shown to reduce breast cancer risk, but the degree of risk reduction is uncertain. In addition to these factors, at this point in time, the other thing that younger women can do is understand their family history.
18. What is the Breast Cancer Risk Assessment Tool?
There are several tools to assess breast cancer risk. One of them, the Breast Cancer Risk Assessment Tool, is a computer program that was developed by scientists at the NCI and the National Surgical Adjuvant Breast and Bowel Project to assist health care providers in discussing breast cancer risk with their female patients. The tool allows a health professional to project a woman's individual estimate of breast cancer risk over a 5-year period of time and over her lifetime and compares the woman's risk calculation with the average risk for a woman of the same age. The Breast Cancer Risk Assessment Tool can be found at http://www.cancer.gov/bcrisktool/. Also note that a model to enhance risk assessment among African American women was incorporated into this tool in 2008.
19. What about interval cancers, or those that occur between screenings?
The interval cancer rate (ICR) is an important indicator of how well a screening program is working in actually detecting cancer. An interval breast cancer is defined as breast cancer diagnosed within one or two years following a negative screening examination. Interval breast cancers are an expected occurrence since mammography does not identify all cancers. The size of the interval cancer rate is sometimes used as a measure of quality, but many factors can affect these rates.
Screening mammography programs can vary in how they enroll women, recommended screening intervals, number of views of the breast taken, reading procedures, and performance. In examining screening programs, considerable variation in general health care systems within Europe and also between Europe and the U.S. have been found.
A 2009 study compared the ICR in Norway and North Carolina, two places that have population registration for documentation of cancer following screening mammography. The definition and accounting of interval cancers were uniform in both locales but the study found that breast cancer rates were lower in Norway compared with North Carolina. A substantially lower rate and proportion of DCIS were found in Norway than in North Carolina.
The observed differences in the ICR between the two locations are likely due to reasons such as program organization, recommended screening intervals, individual screening histories, reading procedures, and screening performance.
[Reference: Journal of Medical Screening, 2009; Vol. 16. Pages 131-139]
Section 3: Breast Cancer Research
20. How is NCI supporting efforts to find better ways to prevent and treat breast cancer?
NCI conducts and supports ongoing breast cancer research that ranges from basic science through the full spectrum of clinical care.
· Basic research--Researchers are trying to identify the causes of breast cancer, including the role of gene changes or variations beyond those identified in BRCA1 and BRCA2. Scientists are also investigating how hormonal, dietary, and environmental factors might contribute to the development of breast cancer. There is also a substantial effort to understand biologic differences in cancer development among African American and other populations.
· Prevention--As a result of NCI-supported research, the drugs tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women who are at high risk for the disease; tamoxifen can be used by both premenopausal and postmenopausal women, whereas raloxifene is appropriate for postmenopausal women only. Currently, researchers are looking for additional ways to prevent breast cancer in women who are at increased risk. They are studying how changes in diet, physical activity, nutrition, and environmental factors may lead to a reduced risk of developing breast cancer.
· Early detection and diagnosis--Researchers are conducting several studies to find better ways of detecting and diagnosing breast cancer so women can receive treatment sooner. NCI-funded research is also using modeling to estimate the effects of screening on subpopulations like African-Americans.
· Treatment--Numerous studies are being conducted to find more effective and less toxic treatments for breast cancer, better ways to deal with the symptoms of this disease and the side-effects of its treatment, and new approaches to improve the quality of life of breast cancer patients and survivors. Scientists are working on developing more personalized therapies that directly target a woman's individual cancer, sparing other parts of the body from harmful side-effects or sparing her from the use of toxic drugs that are unlikely to work against her particular cancer. Investigators are evaluating various breast imaging techniques and their ability to enhance the screening, diagnosis, staging and response to therapy.
21. What studies are looking at ways to better understand the genetic underpinnings of breast cancer?
There are many studies related to breast cancer at NCI as well as at other Federal and private research facilities. That investment goes into several areas including basic science, prevention, early detection, epidemiology, genetics, and treatment.
One set of studies relevant to understanding the genetic underpinnings of breast cancer sponsored by NCI is called CGEMS, which stands for Cancer Genetic Markers of Susceptibility. This is an effort to identify genetic alterations that make people susceptible to breast cancer. By scanning a person's DNA for common genetic differences, researchers compare genes between women who have breast cancer and those who do not. NCI is also sponsoring a Breast Cancer Pre-malignancy Program that is exploring how cancer develops.
The Cancer Genome Atlas (TCGA) pilot project at the National Institutes of Health (NIH) was initiated in 2006 as a comprehensive and coordinated effort to accelerate an understanding of the molecular basis of cancer through the application of genetic technologies. It is being expanded in 2010 to include breast cancer and other cancers, based on the success of the pilot efforts in three types of cancers.
Ongoing studies that explore the biologic basis of cancer have found evidence linking the development of breast cancer, in many cases, with exposure to the hormone estrogen.
22. How is NIH, in particular, investing in research in improved breast cancer screening as well as treatment of breast cancer once it has been diagnosed?
The Breast Cancer Surveillance Consortium (BCSC) is an ongoing effort funded by NCI to improve understanding of breast cancer screening practices in the United States and their relation to changes in stage at diagnosis, survival, and breast cancer mortality. There are five BCSC sites around the United States (Seattle; San Francisco; Burlington, Vt.; Lebanon, N.H.; and Chapel Hill, N.C.) that collect data in the course of clinical care at networks of radiology facilities. This initiative was started in 1994 after Medicare began to fund mammography and there was concern scientists did not know the quality of mammography being delivered in the United States.
NCI has a substantial investment in treatment, including two key examples of where research is ongoing:
· Trial Assigning Individualized Options for Treatment Rx (TAILORx) is determining whether genes associated with a risk of recurrence in women with early-stage breast cancer can be used to identify the most appropriate and effective treatments for these women.
· Specialized Programs of Research Excellence (SPOREs) include 10 breast cancer SPOREs, which move laboratory results to clinical settings with each taking a specific focus. For example, the University of California San Francisco SPORE is considering early biomarkers of risk and biologic determinants of breast density.
Section 4: Breast Cancer Statistics
23. What are the chances that a woman in the United States might develop breast cancer?
Age is the most important risk factor for breast cancer. The older a woman is, the greater her chance of developing breast cancer. Most breast cancers occur in women over the age of 50. The number of cases is especially high for women over age 60. Breast cancer is relatively uncommon in women under age 40. The NCI fact sheet Probability of Breast Cancer in American Women provides more information about lifetime risk. This fact sheet is available at http://www.cancer.gov/cancertopics/factsheet/Detection/probability-breast-cancer.
The incidence of breast cancer is highest in whites, but African Americans have higher mortality rates than any other racial or ethnic group in the United States. The gap in mortality between African Americans and whites is wider now than it was in the early 1990s.
Sixty percent of breast cancer cases are diagnosed while the cancer is still confined to the primary site (localized stage); 33 percent are diagnosed after the cancer has spread to regional lymph nodes or directly beyond the primary site; 5 percent are diagnosed after the cancer has already metastasized (distant stage), and for the remaining 2 percent the staging information was unknown. The corresponding 5-year relative survival rates were: 98.3 percent for localized; 83.5 percent for regional; 23.3 percent for distant; and 57.7 percent for unstaged breast cancers.
24. How many women will develop breast cancer in 2009 and how many will die of the disease?
Breast cancer is the most frequently diagnosed non-skin cancer in American women. An estimated 194,000 American women will be diagnosed with breast cancer in 2009 and an estimated 41,000 people will die of the disease. This includes about 400 breast cancer deaths in men, or about one percent of all breast cancer deaths.
25. What factors might contribute to the higher breast cancer death rate observed in African American women?
Lack of medical coverage, barriers to early detection and screening, and unequal access to improvements in cancer treatment may contribute to observed differences in survival between African American and white women. In addition, recent NCI-supported research indicates that aggressive breast tumors are more common in younger African American and Hispanic women. This more aggressive form of breast cancer is less responsive to standard cancer treatments and is associated with poorer survival.
26. What is the appropriate measure of screening effectiveness?
Reduction in breast cancer mortality (deaths from breast cancer) is the accepted measure of screening effectiveness. Where screening is concerned, assessing improvements in the survival from the time of diagnosis misrepresents the benefit because it is confounded by several biases peculiar to screening:
· Lead-time bias: Breast-cancer-specific survival is measured from the time of diagnosis of breast cancer to the time of death. If a breast cancer is screen-detected before symptoms, then the lead time in diagnosis equals the length of time between screening detection and when the first signs/symptoms would have appeared. Even if early treatment had no benefit, the survival of screened persons is longer simply by the addition of the lead time. For that reason, the assessment of a screening test's benefit cannot be determined by the comparison of survival times. The evaluation of any screening test is best done in randomized trials before the test is approved for general use. In a randomized trial, people who choose to be in the trial are randomly assigned to be offered the test or not. These trials involve thousands of people and allow the comparison of mortality among those offered the test compared to those who were not offered the test.
· Length bias refers to the tendency of the screening test to detect cancers that take longer to become symptomatic; that is, the more indolent, slow-growing cancers. Not all cancers have the same behavior; some are very aggressive, whereas many breast cancers grow more slowly. The cancers that grow slowly are easier to detect because they have a longer pre-symptomatic period when they are detectable. Thus, the screening test detects more slow-growing cancers than fast-growing cancers. Patients with screen-detected cancers survive longer in part because the screened cancers are more indolent, but the improved survival cannot be accurately attributed to the early treatment and does not characterize the behavior of the cancer in general because screening, by its nature, has found the slow growing tumors.
· Over-diagnosis bias is the recognition that screening may detect a condition that is not lethal cancer or may not affect a person's life. This benign process, sometimes called pseudo-disease, is a tumor one dies with and not from. It looks like cancer both to the naked eye and under the microscope, but it does not have the potential to kill. Over-diagnosis bias occurs when a screening test detects a tumor that when removed appears to have been treated successfully, making the screening test look effective when, in fact, the test detected something nonlethal.
There are other biases that render survival an ineffective measure of screening benefit, but lead-time, length, and over-diagnosis bias are the most important and are widely appreciated. It is for this reason that breast cancer-specific mortality (the number of breast cancer deaths among those screened) has remained a highly valid measure of screening benefit; it circumvents these biases.
27. Is the count, or number of deaths due to breast cancer, an accurate measure of mammography's effectiveness?
It is important to note that something called a case fatality rate cannot be used as a measure of screening effectiveness because this measurement does not eliminate these biases. Case fatality rate refers to number of deaths occurring among those with breast cancer. As such, case fatality rate includes the very slow growing cancers (length bias) and benign-behaving cancers (over-diagnosis bias) detected by screening, for which outcomes are expected to be very good. Case fatality rates misrepresent screening benefit by making screen-detected breast cancer appear to result in better outcomes, when, in fact, the overall death rates in the screened population (mortality rate) may not improve.
28. What is the difference between absolute and relative risk?
Most discussion of breast cancer risk centers around absolute risk.
· Absolute risk: These risks are not compared to any other risk. They are just the probability of something occurring. They may be expressed as percentages, or as ratios. For example:
· the risk of getting breast cancer in a woman's lifetime is currently estimated at 12.08 percent, or about one in eight
· the risk of dying of breast cancer in a woman's lifetime is currently estimated at 2.84 percent, or about 1 in 35
· the risk of a 40 year old woman who has never had breast cancer being diagnosed with the disease in the next 10 years is currently estimated at 1.44 percent, or about 1 in 70
· the risk of a 50 year old woman who has never had breast cancer being diagnosed with the disease in the next 10 years is currently estimated to be 2.39 percent, or 1 in 42
· the risk of a 60 year old women who has never had breast cancer being diagnosed with the disease · in the next 10 year is currently estimated at 3.56 percent, or about 1 in 28.
· Relative risk: This is a comparison between different risk levels. For example, your relative risk for lung cancer is (approximately) 10 if you have ever smoked, compared to a nonsmoker. This means you are 10 times as likely to get lung cancer if you have been a smoker. If the risk is about one percent for a nonsmoker, this translates to about 10 percent for a person who has smoked (it is even higher for heavy smokers).
The relative risk (or risk ratio) is not the same as an increase in risk. For example, the relative risk of smoking is a factor of 10, but this means that the increase is by a factor of nine. In other words, a 900 percent increase is the same as the relative risk of 10. Similarly, a risk ratio of 2 means a 100 percent increase (the risk gets multiplied by 2).
The difference is perhaps more evident when the risk increase is small. If a high fat diet has a risk ratio of 1.65 for colorectal cancer in men, this is a 65 percent increase compared with men who have a low-fat diet. The comparison group is considered 1. If the relative risk is 1, this means that there is no increased risk.
An important feature of relative risk is that it tells you nothing about the actual risk. This can be very important for evaluating how significant a relative increase might be. A small increase in risk in a large population can result in many deaths. For example, brain tumors are diagnosed in about 6 per 100,000 persons per year, whereas malignant breast cancer is diagnosed in about 134 per 100,000 people. A 10 percent increase (relative risk of 1.1) in brain tumors means .10 x 6 = .6 new cases per 100,000 people. On the other hand, a 10 percent increase in breast cancer means that an additional 13.4 per 100,000 people are affected.
29. How did you determine the 'number needed to screen' for mammography studies?
The number needed to screen (NNS) is a summary population measure used in assessing the effectiveness of a health-care intervention such as mammography. The NNS takes into account both the characteristics of the screening test, as well as the effectiveness of the treatments available. This measure is the number of people who need to be screened in order to prevent one additional death due to breast cancer. The higher the NNS, the more people who must be screened in order to impact one person's lifespan.
30. Please explain some statistical and other terms
· Survival refers to the number of people remaining alive at a certain point in time relative to diagnosis. For example, a five-year survival of 60 percent means that 60 percent of people will be alive five years from diagnosis. Survival is the most important measure used to compare different methods of treatment to one another. People with the same disease and severity of disease are treated with different agents (or in different ways); their survival is measured to determine which treatment is associated with longer survival.
· Mortality refers to the number of deaths from the disease within the population screened:
[# Deaths / # Individuals Screened Overall]
Case fatality rate refers to the number of deaths from the disease within the population having the disease: [# Deaths / # Individuals with Breast Cancer]
· Case fatality rate cannot be used to measure screening effectiveness because it does not account for screening biases.
Cure: Most commonly defined as disease-free survival to five years. This is an imprecise term that can be highly confusing. It is frequently misinterpreted as meaning permanently cancer-free.
31. Related NCI Web pages:
NCI's breast cancer Web site:
NCI's Physician Data Query (PDQ) breast cancer screening page:
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