Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about breast cancer screening. This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board.
Information about the following is included in this summary:
This summary is intended as a resource to inform clinicians and other health professionals about currently available breast cancer screening modalities. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in reporting the evidence of benefit and potential harms associated with each screening modality. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language.
Summary of Evidence
Note: Separate PDQ summaries on Breast Cancer Prevention; Breast Cancer Treatment; Male Breast Cancer Treatment; and Breast Cancer Treatment and Pregnancy are also available.
Screening by Mammography
Statement of benefit
Based on fair evidence, screening mammography in women aged 40 to 70 years decreases breast cancer mortality. The benefit is higher for older women, in part because their breast cancer risk is higher.
Statement of harms
Based on solid evidence, screening mammography may lead to the following harms:
Table 1. Harms of Screening Mammography
|Harm||Study Design||Internal Validity||Consistency||Magnitude of Effects||External Validity|
|Treatment of insignificant cancers (overdiagnosis, true positives) can result in breast deformity, lymphedema, thromboembolic events, new cancers, or chemotherapy-induced toxicities.||Descriptive population-based, autopsy series and series of mammary reduction specimens||Good||Good||Approximately 33% of breast cancers detected by screening mammograms represent overdiagnosis.||Good|
|Additional testing (false-positives)||Descriptive population-based||Good||Good||Estimated to occur in 50% of women screened annually for 10 years, 25% of whom will have biopsies.||Good|
|False sense of security, delay in cancer diagnosis (false-negatives)||Descriptive population-based||Good||Good||6% to 46% of women with invasive cancer will have negative mammograms, especially if young, with dense breasts, or with mucinous, lobular, or fast-growing cancers.||Good|
|Radiation-induced mutations can cause breast cancer, especially if exposed before age 30 years. Latency is more than 10 years, and the increased risk persists lifelong.||Descriptive population-based||Good||Good||Between 9.9 and 32 breast cancers per 10,000 women exposed to a cumulative dose of 1 Sv. Risk is higher for younger women.||Good|
Screening by Clinical Breast Examination
Statement of benefits
Based on fair evidence, screening by clinical breast examination reduces breast cancer mortality.
Statement of harms
Based on solid evidence, screening by clinical breast examination may lead to the following harms:
Table 2. Harms of Screening Clinical Breast Examination
|Harms||Study Design||Internal Validity||Consistency||Magnitude of Effects||External Validity|
|Additional testing (false-positives)||Descriptive population-based||Good||Good||Specificity in women aged 50 to 59 years ranged between 88% and 96%.||Good|
|False reassurance, delay in cancer diagnosis (false-negatives)||Descriptive population-based||Good||Fair||Of women with cancer, 17% to 43% had a negative clinical breast examination.||Poor|
Screening by Breast Self-Examination
Statement of benefit
Based on fair evidence, teaching breast self-examination does not reduce breast cancer mortality.
Statement of harms
Based on solid evidence, formal instruction and encouragement to perform breast self-examination leads to more breast biopsies and to the diagnosis of more benign breast lesions.
1. Nyström L, Andersson I, Bjurstam N, et al.: Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 359 (9310): 909-19, 2002.
2. Shapiro S: Periodic screening for breast cancer: the Health Insurance Plan project and its sequelae, 1963-1986. Baltimore, Md: Johns Hopkins University Press, 1988.
3. Miller AB, To T, Baines CJ, et al.: The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med 137 (5 Part 1): 305-12, 2002.
4. Miller AB, Baines CJ, To T, et al.: Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 147 (10): 1477-88, 1992.
5. Moss SM, Cuckle H, Evans A, et al.: Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet 368 (9552): 2053-60, 2006.
6. Zahl PH, Strand BH, Maehlen J: Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 328 (7445): 921-4, 2004.
7. Elmore JG, Barton MB, Moceri VM, et al.: Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 338 (16): 1089-96, 1998.
8. Rosenberg RD, Hunt WC, Williamson MR, et al.: Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico. Radiology 209 (2): 511-8, 1998.
9. Kerlikowske K, Grady D, Barclay J, et al.: Likelihood ratios for modern screening mammography. Risk of breast cancer based on age and mammographic interpretation. JAMA 276 (1): 39-43, 1996.
10. Porter PL, El-Bastawissi AY, Mandelson MT, et al.: Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 91 (23): 2020-8, 1999.
11. Ronckers CM, Erdmann CA, Land CE: Radiation and breast cancer: a review of current evidence. Breast Cancer Res 7 (1): 21-32, 2005.
12. Goss PE, Sierra S: Current perspectives on radiation-induced breast cancer. J Clin Oncol 16 (1): 338-47, 1998.
13. Baines CJ, Miller AB, Bassett AA: Physical examination. Its role as a single screening modality in the Canadian National Breast Screening Study. Cancer 63 (9): 1816-22, 1989.
14. Thomas DB, Gao DL, Ray RM, et al.: Randomized trial of breast self-examination in Shanghai: final results. J Natl Cancer Inst 94 (19): 1445-57, 2002.
Incidence and Mortality
Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 184,450 new cases of invasive disease (plus 67,770 cases of in situ disease) and 40,930 deaths in 2008.  Males account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section of this summary for more information).
Ecologic studies from the United States  and the United Kingdom  demonstrate an increase in breast cancer incidence over the last 3 decades, rising from 82 cases per 100,000 people in 1973 to 118 per 100,000 in 1998. Between 1970 and the early 1980s the increase was small and has been attributed to changes in reproductive behavior and hormone use. Since the mid-1980s, with the widespread adoption of screening mammography, the increase has been dramatic. By illustration, the incidence among British women aged 50 to 65 years nearly doubled between 1984 and 1994. Similarly, in Sweden, where more cancers are discovered in younger women, the incidence of breast cancer increased dramatically in counties that adopted screening.  Similar findings have been documented in the United States. Mammographic screening has also increased the diagnosis of noninvasive cancers and premalignant lesions. Whereas ductal carcinoma in situ was a rare condition before 1985, it is currently diagnosed in more than 55,000 American women per year (refer to the Ductal Carcinoma In Situ section of this summary for more information).
One might expect that screening will identify many cancers before they cause clinical symptoms, followed by a subsequent compensatory decline in cancer rates, seen either in annual population incidence rates or in incidence rates in older women. So far, no compensatory drop in incidence rates attributable to a change in screening patterns has been observed. This raises concerns about overdiagnosis—screening that identifies clinically insignificant cancers (refer to the Overdiagnosis section of this summary for more information).
The risk of breast cancer depends on age (see Table 3). The commonly cited lifetime risk of one in seven women is misleading because it expresses a cumulative lifetime risk, spread over 100 years. As seen in Table 3, the risk of an average 40-year-old woman developing breast cancer in the next 10 years is approximately 1.5% (less than 1 in 60). This statistic, however, includes 40-year-old women of all risk groups, without regard to their use of screening mammograms. Therefore, a 40-year-old woman without any risk factors will have a lower risk of being diagnosed with breast cancer. Her risk is lower if she recently had a normal mammogram, and it is lower if she forgoes mammography (because of overdiagnosis) (see below).
Table 3. Probability of Developing Invasive Breast Cancer Among Womena
|Current Age (in Years)b||Risk Interval (in Years)c|
|30||0.40%||1.85%||4.56%||13.48% (1 in 7)|
|40||1.47%||4.21%||7.53%||13.24% (1 in 8)|
|50||2.84%||6.25%||9.68%||12.16% (1 in 8)|
|60||3.67%||7.35%||9.54%||10.00% (1 in 10)|
|aBased on an analysis of data from the Surveillance, Epidemiology, and End Results registry for 1997–1999.|
|bWomen who are free from invasive breast cancer at their current age.|
|cShown as risk over specific intervals of time.|
In 2008, an estimated 40,480 women will die of breast cancer, compared with about 71,030 women who will die of lung cancer.  Approximately one in six women diagnosed with breast cancer dies of the breast cancer, while nearly all women with lung cancer die of lung cancer.
Breast cancer mortality increases with age. For a 40-year-old woman without a breast cancer diagnosis, the chance of dying from breast cancer within the next 10 years is extremely small, but for a woman older than 65 years, it is about 1% (see Table 4). Women older than 70 years have an even higher risk of dying of breast cancer, but they are even more likely to die of other causes. 
Table 4. Mortality Risk According to Age: Breast Cancer and All Causesa
|For Women Aged:||Chance of Dying of Breast Cancer in the Next 10 Years||Chance of Dying From Any Cause in the Next 10 Years|
|40–44||0.3% (1 in 333)||2.1% (1 in 48)|
|45–49||0.4% (1 in 250)||3.3% (1 in 30)|
|50–54||0.6% (1 in 167)||5.1% (1 in 20)|
|55–59||0.7% (1 in 143)||8.1% (1 in 12)|
|60–64||0.8% (1 in 125)||12.0% (1 in 8)|
|65–69||1.0% (1 in 100)||18.0% (1 in 6)|
|70–74||1.1% (1 in 91)||27.0% (1 in 4)|
|75–79||1.2% (1 in 83)||41.0% (1 in 2)|
|80–84||1.2% (1 in 83)||67.0% (2 in 3)|
|85+||1.1% (1 in 91)||79.0% (4 in 5)|
|aAdapted from Woloshin & Schwartz, 1999.|
Other Risk Factors
Additional risk factors include a strong family history of breast or ovarian cancer (particularly first-degree relatives, on either the mother's or father's side); early age at menarche and late age at first birth (reflecting estrogen exposure); and a history of breast biopsies, especially for proliferative benign breast disease,   including radial scalloping lesions (a pathologic entity also called radial scars, even though unrelated to previous surgeries or scars).  The Gail Model estimates individual risk over time based on these factors for women aged 40 years or older who receive regular mammography.    (Refer to the Breast Cancer Risk Assessment Tool.)
Women with a personal history of invasive breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ have a 0.6% to 1.0% estimated annual risk of developing a new primary breast cancer. 
Women treated with thoracic radiation, especially when younger than 30 years, have a 1% annual risk of breast cancer, starting 10 years after the irradiation. 
Radiological breast density    is a strong risk factor for breast cancer and also presents challenges in the interpretation of mammograms. Dense fibroglandular tissue seen on mammography is associated with a threefold to sixfold increased risk of breast cancer compared with fatty breast tissue.
Behavioral factors such as menopausal hormone use, obesity, and alcohol intake are associated with an increased risk of breast cancer. (Refer to the PDQ summaries on Cancer Prevention Overview and Prevention of Breast Cancer for more information.)
Breast cancer incidence and mortality risk also vary according to geography, culture, race, ethnicity, and socioeconomic status and are discussed more fully below (refer to the Special Populations section of this summary for more information).
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10. Gail MH, Brinton LA, Byar DP, et al.: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81 (24): 1879-86, 1989.
11. Bondy ML, Lustbader ED, Halabi S, et al.: Validation of a breast cancer risk assessment model in women with a positive family history. J Natl Cancer Inst 86 (8): 620-5, 1994.
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14. Goss PE, Sierra S: Current perspectives on radiation-induced breast cancer. J Clin Oncol 16 (1): 338-47, 1998.
15. Ma L, Fishell E, Wright B, et al.: Case-control study of factors associated with failure to detect breast cancer by mammography. J Natl Cancer Inst 84 (10): 781-5, 1992.
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Breast Cancer Diagnosis
Evaluation of Breast Symptoms
Breast symptoms may suggest a diagnosis of breast cancer. During a 10-year period, 16% of 2,400 women aged 40 to 69 years sought medical attention for breast symptoms at their health maintenance organization.  Women younger than 50 years were twice as likely to seek evaluation. Additional examinations were performed in 66% of patients, with 27% undergoing invasive procedures. Cancer was diagnosed in 6.2% of patients with breast symptoms, most being stage II or III. Of the breast symptoms prompting medical attention, a mass was most likely to lead to a cancer diagnosis (10.7%) and pain was least likely (1.8%) to do so.
Pathologic Diagnosis of Breast Cancer
Breast cancer is diagnosed by pathologic review of a fixed specimen of breast tissue. The breast tissue can be obtained from a symptomatic area or from an area identified by a screening test, usually mammography. A palpable lesion can be excised surgically or biopsied with fine-needle aspirate or core needle biopsy (CNBx). Nonpalpable lesions can be excised by surgical needle localization under x-ray guidance (SNLBx). Alternatively, a CNBx of a mammographically suspicious area can be obtained with use of stereotactic x-ray or ultrasound. In a retrospective study of 939 patients with 1,042 mammographically detected lesions who underwent CNBx or SNLBx, sensitivity for malignancy was greater than 95% and the specificity was greater than 90%. Compared with SNLBx, CNBx resulted in fewer surgical procedures for definitive treatment with a higher likelihood of clear surgical margins at the initial excision. 
Fine-needle aspiration, nipple aspiration, and ductal lavage are three methods of obtaining cells from breast tissue or ductal epithelium for cytological examination (see Tissue Sampling [Fine-Needle Aspiration, Nipple Aspirate, Ductal Lavage]).
None of these technologies has been tested in controlled trials of screening or compared with other breast cancer screening modalities.
Ductal Carcinoma In Situ
Ductal carcinoma in situ (DCIS) is a noninvasive condition that can progress to invasive cancer, with variable frequency and time course. While some authors include DCIS with invasive breast cancer statistics, it has been suggested that the term DCIS be replaced by a classification system of ductal intraepithelial neoplasia (DIN), similar to those used to grade cervical and prostate precursor lesions. DCIS is usually diagnosed by mammography, so it is rare in unscreened women. In the United States in 1983, the prescreening era, 4,900 women were diagnosed with DCIS, compared with 67,770 that will be diagnosed in 2008. 
The natural history of untreated DCIS is poorly understood because women diagnosed with DCIS undergo surgery, with or without radiation and hormone therapy. According to data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute on women with newly diagnosed DCIS treated between 1984 and 1989, 1.9% died of breast cancer within 10 years of diagnosis.  Development of breast cancer after treatment of DCIS varies according to treatment. One large randomized trial found that 13.4% of women treated by lumpectomy alone developed ipsilateral invasive breast cancer by 90 months, compared with 3.9% of those treated by lumpectomy and radiation.  Another series of 706 DCIS patients, however, allowed definition of the University of Southern California/Van Nuys Prognostic Scoring Index, which defines the risk of recurrence based on age, margin width, tumor size, and grade.  The low-risk group, comprising a third of the cases, experienced few DCIS recurrences (1%) and no invasive cancers, regardless of whether radiation was given. The moderate- and high-risk groups had higher recurrence rates, with a beneficial preventive effect of radiation. Nonetheless, only approximately 1% had death from breast cancer. The addition of tamoxifen also reduces the incidence of invasive breast cancer after excision of DCIS.  Because all these studies include excision of mammographically detected DCIS, the natural history of this condition remains unknown.
Some information about the natural history of untreated, palpable DCIS is available. A retrospective review of 11,760 biopsies performed between 1952 and 1968 identified 28 cases of untreated DCIS (noncomedo type).   All were found by clinical examination, underwent biopsy only, and were followed for 30 years. Nine women (32%) developed invasive breast cancer in the area of previous DCIS. Of these, seven cancers were diagnosed within 10 years of DCIS biopsy, and two were diagnosed between 10 and 30 years after biopsy. Many of the cancers were diagnosed at advanced stages, possibly because of the false reassurance of the previous “negative” biopsy. None of the women with invasive cancer received adjuvant systemic therapy. Four eventually died of the disease. These findings have been used as an argument both for and against aggressive diagnosis and treatment of DCIS.
Many DCIS cases will not progress to invasive cancer, and those that do are likely to be managed successfully at the time of progression. Thus, treatment of all screen-detected DCIS with surgery, radiation, and/or hormone therapy represents overdiagnosis and overtreatment for many. The Canadian National Breast Screening Study-2 of women aged 50 to 59 years found a fourfold increase in DCIS cases in women screened by clinical breast examination plus mammography compared with those screened by clinical breast examination alone, with no difference in breast cancer mortality.  (Refer to the PDQ summary on Breast Cancer Treatment for more information.)
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Breast Cancer Screening Modalities
Mammography utilizes ionizing radiation to image breast tissue. The examination is performed by compressing the breast firmly between a plastic plate and an x-ray cassette that contains special x-ray film. For routine screening, examination films are taken in mediolateral oblique and craniocaudal projections. Both views should include breast tissue from the nipple to the pectoral muscle. Two-view examinations decrease the recall rate compared with single-view examinations by eliminating concern about abnormalities due to superimposition of normal breast structures. 
Under the Mammography Quality Standards Act (MQSA) enacted by Congress in 1992, all facilities that perform mammography must be certified by the U.S. Food and Drug Administration (FDA). This mandate has resulted in improved mammography technique, lower radiation dose, and better training of personnel. Refer to the list of FDA Certified Mammography Facilities. Image contrast has improved with the use of lower voltage, specialized aluminum grids, and higher film optical density. The 1998 MQSA Reauthorization Act requires that patients receive a written lay-language summary of mammography results.
Mammography can identify breast cancers too small to palpate on physical examination and can also find ductal carcinoma in situ (DCIS), a noninvasive condition. Because all cancers develop as a consequence of a series of mutations, it is theoretically beneficial to diagnose these noninvasive lesions. A large increase in the frequency of DCIS diagnosis occurred in the United States beginning in the early 1980s  because of the increased use of screening mammography. Appropriate management of DCIS is not well understood because its natural history is incompletely defined. (Refer to the PDQ summary on Breast Cancer Treatment for more information. Also refer to the Ductal Carcinoma in Situ section of this summary.)
Numerous uncontrolled trials and retrospective series have documented the capacity of mammography to diagnose small, early-stage breast cancers, including those that have a favorable clinical course.  These trials also show that cancer-related survival is better in screened women than in nonscreened women. These comparisons are susceptible, however, to a number of important biases:
Because the extent of these biases is never clear in any particular study, one must rely on randomized controlled trials to assess the benefits of screening. (Refer to the Effect of Screening on Breast Cancer Mortality section.)
The sensitivity of mammography is the proportion of breast cancer detected when breast cancer is present. Sensitivity depends on several factors, including lesion size, lesion conspicuity, breast tissue density, patient age, the hormone status of the tumor, overall image quality, and interpretive skill of the radiologist. Sensitivity is of great importance to patients and physicians alike; failure to diagnose breast cancer is the most common cause of medical malpractice litigation. Half of the cases resulting in payment to the claimant had false-negative mammograms. 
Overall sensitivity is approximately 75%  but ranges from 54% to 58% in women younger than 40 years to 81% to 94% in those older than 65 years.   Using data from screened women in the Group Health Cooperative of Puget Sound health maintenance organization, characteristics of 150 cancers not detected at screening but diagnosed within 24 months of a normal screening examination (interval cancers) were compared with those of 279 screen-detected cancers. Interval cancers were much more likely to occur in women younger than 50 years and to be of mucinous or lobular histology, high histologic grade, and high proliferative activity. Screen-detected cancers were more likely to have tubular histology; to be smaller, of low stage, and hormone sensitive; and to have a major component of in situ cancer. 
Mammography is a less sensitive test for women aged 40 to 49 years than for older women. The authors of one study examined 576 women who developed invasive breast cancer following a screening mammogram to determine whether greater breast density or faster growing tumors among younger women explained the lower sensitivity. They found that more younger women with cancer had developed interval cancers. They also found that greater breast density explained most (68%) of the decreased mammographic sensitivity in younger women at 12 months, whereas at 24 months, rapid tumor growth and breast density explained approximately equal proportions of the interval cancers. 
It is widely accepted that screen-detected cancers have a more favorable prognosis. This may be related to length bias, true benefit of screening, or both in finding cancers at an earlier stage of development. It is also known that screen-detected cancers have favorable cellular characteristics, including lower histologic grade, higher rate of hormone sensitivity, and lower proliferative indices. A 10-year follow-up study of 1,983 Finnish women with invasive breast cancer demonstrated that the method of cancer detection is an independent prognostic variable. When controlled for age, node involvement, and tumor size, screen-detected cancers had a lower risk of relapse and better overall survival. The hazard ratio for death was 1.90 (95% confidence interval [CI], 1.15–3.11) for women whose cancers were detected outside screening, even though they were more likely to get adjuvant systemic therapy. Similarly, an examination of the breast cancers found in three randomized screening trials (Health Insurance Plan, National Breast Screening Study (NBSS)-1, and NBSS-2—see below) accounted for stage, nodal status, and tumor size and determined that patients whose cancer was found via screening enjoyed a more favorable prognosis. Namely, the hazard ratios for death were 1.53 (95% CI, 1.17–2.00) for interval and incident cancers in comparison with screen-detected cancers and 1.36 (95% CI, 1.10–1.68) for cancers in the control group in comparison with screen-detected cancers.  Thus, method of cancer detection seems to be a powerful predictor of patient outcome above and beyond traditional patient and tumor characteristics. 
A critical factor determining mammographic sensitivity is the radiologist’s interpretation. Studies have shown substantial variability in interpretation and reading accuracy among radiologists.          The studies that have been conducted using physician interpretation of actual mammograms suggest that sensitivity, specificity, or both increase with higher volume of mammograms read by a radiologist.    Whether this results from different overall accuracy or a shift in the trade-off between sensitivity and specificity, however, is not certain. The clinical significance of variability in radiologists' interpretations is not clear.  Identifying a radiologist who is more accurate than another is difficult.
High breast density is associated with low sensitivity. At all ages, regardless of hormone replacement therapy (HRT), also called hormone therapy (HT), high breast density is associated with 10% to 29% lower sensitivity.  HT therapy, which increases breast density is associated with both lower sensitivity and an increased rate of interval cancers.  High breast density is an inherent trait, which can be familial   but also may be affected by age, endogenous  and exogenous   hormones,  selective estrogen receptor modulators such as tamoxifen,  and diet.  Strategies have been proposed to improve mammographic sensitivity by altering diet, by timing mammograms with menstrual cycles, or by interrupting HRT/HT use before the examination.
The specificity of mammography is the likelihood of the test being normal when cancer is absent, whereas the false-positive rate is the likelihood of the test being abnormal when cancer is absent. If specificity is low, many false-positive examinations result in unnecessary follow-up examinations and procedures. (Refer to the Harms of Screening section.) An improvement in reporting mammography results has been the adoption of Breast Imaging Reporting and Data System (BI-RADS) categories, which standardize the terminology used in assessing the significance of the findings and recommending future action. A study correlating needle localization biopsies with BI-RADS categories showed that categories 0 and 2 yielded benign tissue in 87% and 100%, respectively, of 65 cases. Category 3 (probably benign) yielded benign tissue in 98% of 141 cases, category 4 (suspicious) yielded benign tissue in 70% of 936 cases, and category 5 (highly suspicious) yielded benign tissue in only 3% of 170 cases.  Studies have shown relatively little impact of false-positive test results on the use of subsequent mammography screening behavior, but false-positive test results may have long-term consequences, such as anxiety about breast cancer. 
International comparisons of screening mammography have found that specificity is greater in countries with more highly centralized screening systems and national quality assurance programs.   For example, one study reported that the recall rate is twice as high in the United States as it is in the United Kingdom, with no difference in the rate of cancers detected.  Such comparisons may be confounded, however, by other social, cultural, or economic factors that can influence the performance of mammography screening.
The Million Women Study in the United Kingdom revealed three patient characteristics that decrease the sensitivity and specificity of screening mammograms in women aged 50 to 64 years: use of postmenopausal HT, prior breast surgery, and body mass index below 25.  Another factor that affects sensitivity and specificity is the interval since the last examination. One study used data from seven registries in the United States to examine mammographic data and cancer outcomes in 1,213,754 screening mammograms in 680,641 women. With longer intervals between mammograms, sensitivity increased, specificity decreased, recall rate increased, and cancer detection rate increased. 
The optimal interval between screening mammograms is unknown, and practice varies widely. A prospective trial that was undertaken in the United Kingdom randomly assigned women aged 50 to 62 years to annual or the standard 3-year interval for screening mammograms. More cancers of slightly smaller size were detected in the annual screening group with a lead time of 7 months; however, the grade and node status were similar in both groups.  A large observational study found a slightly increased risk of late-stage disease at diagnosis for women in their 40s who were adhering to an every-2-year versus every-1-year schedule (28% vs. 21%; OR = 1.35; 95% CI, 1.01–1.81). A 2-year interval was not associated with late-stage disease for women in their 50s or 60s. 
As a general rule, cancers that arise between screening examinations (interval cancers) have characteristics of rapid growth   and are frequently of advanced stage.  The likelihood of diagnosing cancer is highest with the prevalent (first) screening examination, ranging from 9 to 26 cancers per 1,000 screens, depending on age. That likelihood decreases for follow-up examinations, ranging from only one to three cancers per 1,000 screens. 
Most screening mammography in the United States uses screen-film technology. Digital mammography is more expensive but more amenable to data storage and sharing. Performance of both technologies has been compared directly in three trials with similar results.
A large cohort of women undergoing both types of mammography was evaluated at 33 U.S. centers in the Digital Mammographic Imaging Screening Trial, showing no differences in mammographic sensitivity and specificity. Digital mammography had a higher sensitivity in premenopausal and perimenopausal women, in women younger than 50 years, and in women with dense breasts, according to a planned subset analysis. 
An Italian trial of parallel cohorts of 14,385 women matched for age and interpreting radiologist were screened by either full-field digital or screen-film mammography. Recall rate and cancer detection rate, especially for clustered microcalcifications, were higher for digital mammography, whereas the recall rate for poor technical quality was higher for screen-film mammography. There was no difference in positive predictive value (PPV). 
The Oslo II Study randomly assigned women to screening by digital mammography (n = 6,944) versus screen-film mammography (n = 16,985) with soft-copy double reading by experienced radiologists. Recall and cancer detection rates were higher for digital mammography, but there was no difference in PPV or incidence of interval cancers. 
Computer-aided detection (CAD) systems are designed to assist radiologists in reading mammograms. The goal is to help identify suspicious regions such as clustered microcalcifications and masses.  The use of CAD systems increases sensitivity but decreases specificity.  Several CAD systems are in use. However, a large population-based study comparing recall rates and breast cancer detection rates before and after the introduction of CAD systems questions their utility; there was no change in either rate.   Because no mortality studies have been conducted, the impact of CAD on breast cancer mortality is uncertain.
Clinical Breast Examination
No randomized trials of clinical breast examination (CBE) as a sole screening modality have been done. The Canadian National Breast Screening Study compared CBE plus mammography to CBE alone in women aged 50 to 59 years (refer to the Effect of Screening on Breast Cancer Mortality section). CBE was conducted by trained health professionals with periodic evaluations of performance quality. The frequency of cancer diagnosis, stage, interval cancers, and breast cancer mortality were similar in the two groups and compared favorably with other trials of mammography alone. One explanation for this finding was the careful training and supervision of the health professionals performing CBE.  Breast cancer mortality with follow-up 11 to 16 years after entry (mean = 13 years) was similar in the two screening arms (mortality rate ratio, 1.02 [95% CI, 0.78–1.33]).  The investigators estimated the operating characteristics for CBE alone. For 19,965 women aged 50 to 59 years, sensitivity was 83%, 71%, 57%, 83%, and 77% for years 1, 2, 3, 4, and 5 of the trial, respectively, and specificity ranged between 88% and 96%. PPV, which is the proportion of cancers detected per abnormal examination was estimated to be 3% to 4%. For 25,620 women aged 40 to 49 years, who were examined only at entry, the estimated sensitivity was 71%, specificity 84%, and PPV 1.5%.  An analysis of 752,081 CBEs performed between 1995 and 1998 as part of the National Breast and Cervical Cancer Early Detection Program found that 6.9% of CBEs were abnormal and that 3.8 invasive cancers and 1.2 cases of DCIS were detected per 1,000 examinations. Sensitivity was 58.8%, specificity 93.4%, and PPV 4.3%.  A study of screening in women with a positive family history of breast cancer showed that, after a normal initial evaluation, the patient or CBE identified more cancers than did mammography.  Another study examined the usefulness of adding CBE to screening mammography. Among 61,688 women older than 40 years and screened by mammography and CBE, sensitivity and specificity for mammography and for combined mammography-CBE were calculated. Specificity for mammography was 78% and for both modalities 82%. The increased sensitivity was greatest for women aged 60 to 69 years with dense breasts (6.8%), compared with women aged 60 to 69 years with fatty breasts (1.8%). Specificity was lower for women undergoing both screening modalities compared with mammography alone (97% vs. 99%). 
Monthly breast self-examination (BSE) is frequently advocated, but evidence for its effectiveness is weak.   The only large, well-conducted, randomized clinical trial of BSE that has been completed, randomly assigned 266,064 women according to workplace in Shanghai to receive either BSE instruction, reinforcement and encouragement, or instruction on the prevention of lower back pain. Neither group received breast cancer screening through other modalities. After 10 to 11 years of follow-up, 135 breast cancer deaths occurred in the instruction group and 131 in the control group (relative risk [RR] = 1.04; 95% CI, 0.82–1.33). Although the number of invasive breast cancers diagnosed in the two groups was about the same, women in the instruction group had more breast biopsies and more benign lesions diagnosed than did women in the control group. 
Case-control studies, nonrandomized trials, and cohort evidence about the effectiveness of BSE is mixed; results are difficult to interpret because of selection and recall biases. For example, a small case-control study in Seattle, Washington, compared self-reported practice of BSE in women with advanced breast cancer with that in age-matched controls.  The frequency of practicing BSE did not differ in these groups, and there was no decrease in the risk of advanced-stage breast cancer associated with BSE (RR = 1.15; 95% CI, 0.73–1.81). BSE proficiency was low in both groups of women.
In the U.K. Trial of Early Detection of Breast Cancer, two districts invited more than 63,500 women aged 45 to 64 years to educational sessions about BSE. After 10 years of follow-up, there was no difference in mortality rates in these two districts compared with four centers without organized BSE education (RR = 1.07; 95% CI, 0.93–1.22). 
A case-control study nested within the Canadian National Breast Screening Study (NBSS) suggests that well-performed BSE may be effective. This study compared self-reported BSE frequency before enrollment in the trial with breast cancer mortality. Women who examined their breasts visually, used their finger pads for palpation, and used their three middle fingers had a lower breast cancer mortality. 
A device called the Sensor Pad was designed to improve the accuracy of BSE and has been approved by the FDA; however, there is no evidence on its efficacy to decrease breast cancer mortality.
The primary role of ultrasound is the evaluation of palpable or mammographically identified masses. A review of the literature and expert opinion by the European Group for Breast Cancer Screening concluded that “there is little evidence to support the use of ultrasound in population breast cancer screening at any age.” 
Magnetic Resonance Imaging
There is increasing interest in using breast magnetic resonance imaging (MRI) as a screening test for breast cancer among women at elevated risk of breast cancer based on BRCA1/2 mutation carriers, a strong family history of breast cancer, or several genetic syndromes such as Li-Fraumeni or Cowden disease.   Breast MRI is a more sensitive modality for breast cancer detection as compared with screening mammography, but it is also less specific.  
Direct back-to-back comparisons of breast MRI and mammography in young high-risk women report MRI sensitivities ranging from 71% to 100% versus mammography sensitivities of 20% to 50%. The low sensitivities of mammography are consistent with previous experience in young women and those with dense breasts. Contrast-enhancing foci are normal in healthy breasts, and false-positive results are common.   These same studies show that MRI is also associated with threefold to fivefold higher recall rates, higher false-positive rates (with specificities varying from 37%–97%), and substantially worse positive predictive values. Thus, women who are screened with MRI have more negative surgical biopsies. 
It is unknown whether the increase in cancer detection is worthwhile, given the large increase in false-positive rates. All of the published studies are observational studies, and none of the published studies have assessed whether patient outcomes (including morbidity, survival, or mortality) are improved when women are screened with breast MRI.  It is likely that MRI screening may lead to overdiagnosis (i.e., the detection of lesions that would remain asymptomatic in the absence of screening).
Therefore the clinical role of MRI in breast imaging for average-risk women is still reserved for diagnostic evaluation, including evaluating the integrity of silicone breast implants, assessing palpable masses following surgery or radiation therapy, and detecting mammographically and sonographically occult breast cancer in patients with axillary nodal metastasis and preoperative planning for some patients with known breast cancer.
Studies of screening MRI in women of high genetic risk are ongoing.
Scintimammography, using technetium-99m sestamibi or technetium-99m tetrofosmin, scans the axilla and supraclavicular region while simultaneously imaging the breast tissue. In staging women with a known breast cancer, the contralateral arm is injected with the radionuclide, and lateral and anterior projections are imaged with a gamma camera, with both arms raised. The theoretical advantage of this technology is the potential to obtain staging information, but only small clinical series have been described.
Tissue Sampling (Fine-Needle Aspiration, Nipple Aspirate, Ductal Lavage)
Random periareolar fine-needle aspirates were performed in 480 women at high risk for breast cancer, and the women were followed for a median of 45 months.  Twenty women developed breast neoplasms (13 invasive and 7 DCIS). Using multiple logistic regression and Cox proportional hazards analysis, a diagnosis of hyperplasia with atypia was found to be associated with the subsequent development of breast cancer.
Nipple aspirate fluid cytology was studied in 2,701 women who were followed for subsequent incidence of breast cancer, with an average of 12.7 years of follow-up.  Breast cancer incidence overall was 4.4%, including 11 cases of DCIS and 93 of invasive cancer, and was associated with abnormal nipple aspirate fluid cytology. Whereas the breast neoplasm rate was only 2.6% for 352 women in whom no fluid could be aspirated, it was 5.5% for 327 women with epithelial hyperplasia and 10.3% for 58 women with atypical hyperplasia.
One study reported results of nipple aspiration followed by ductal lavage in 507 women at high risk for breast cancer.  Nipple aspirate fluid was obtained from 417 women, but only 111 (27%) were adequate samples. Ductal lavage samples were evaluated in 383 women, 299 (78%) of which were adequate for diagnosis. Abnormal cells were found in 92 (24%) ductal lavage samples, including 88 (17%) with mild atypia, 23 (6%) with marked atypia, and 1 (<1%) malignant. The corresponding numbers and percentages for nipple aspiration fluid were 16 (6%), 8 (3%), and 1 (<1%). Although ductal lavage was associated with some discomfort, it was judged by participants to be comparable to mammography.
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Effect of Screening on Breast Cancer Mortality
The Randomized Controlled Trials
Randomized controlled trials (RCTs), with participation by nearly half a million women from four countries, examined the breast cancer mortality of women who were offered regular screening. One trial (the Canadian National Breast Screening Study [NBSS]-2) compared mammogram plus clinical breast examination (CBE) with CBE alone, but the other eight compared screening mammogram (MMG) with or without CBE with a control consisting of usual care. The trials differed in design, recruitment of participants, interventions (both screening and treatment), management of the control group, compliance with assignment to screening and control groups, and analysis of outcomes. Some trials used individual randomization while others used cluster randomization in which cohorts were identified and then offered screening, and in one case, nonrandomized allocation by day-of-birth in any given month. Cluster randomization sometimes led to imbalances between the intervention and control groups. Age differences have been identified in several trials, although the differences were probably too small to have a major effect on the trial outcome.  In the Edinburgh Trial, socioeconomic status differed markedly between the intervention and control groups. Since socioeconomic status is associated with the risk of breast cancer mortality, this difference makes it difficult, if not impossible, to interpret the trial results.
Since breast cancer mortality is the major outcome parameter for each of these trials, the methods used to determine cause of death is critically important. Efforts to reduce bias in the attribution of mortality cause have been made, including the use of a blinded monitoring committee (New York) and a linkage to independent data sources, such as national mortality registries (Swedish trials). Unfortunately, even these attempts may be unable to avoid prior knowledge of women’s assignment to screening or control arms. Evidence of possible misclassification of breast cancer deaths in the Two-County trial that could bias results in favor of screening has been reviewed. 
Differences exist in the methodology used to analyze the results of these trials. Four of the five Swedish trials were designed to include a single screening mammogram in the control group, timed to correspond with the end of the series of screening mammograms in the study group. The initial analysis of these trials used an “evaluation” analysis, tallying only the breast cancer deaths that occurred in women whose cancer was discovered at or before the last study mammogram. In some of the trials a delay occurred in the performance of the end-of-study mammogram, resulting in more time for control group women to develop or be diagnosed with breast cancer. Other trials used a “follow-up” analysis, which counts all deaths attributed to breast cancer, regardless of the time of diagnosis. This type of analysis was used in a meta-analysis of four of the five Swedish trials in response to previously expressed concerns about the effect of a delay in control group mammograms upon evaluation analyses.
The accessibility of the data for international audit and verification also varies, with formal audit having been undertaken only in the Canadian trials. In fact, the author of one trial (Kopparberg) refused to respond to queries about methodology or to submit raw data for independent review. 
All of these studies are designed to study breast cancer mortality rather than all-cause mortality, because of the infrequency of breast cancer deaths relative to the total number of deaths. When all-cause mortality in these trials was examined retrospectively, only the Edinburgh trial showed a significant difference, which could be attributed to socioeconomic differences. The meta-analysis (follow-up methods) of the four Swedish trials also showed a small but significant improvement of all-cause mortality.
The trials are listed chronologically.
Health Insurance Plan, United States 1963  
Malmo, Sweden 1976  
Ostergotland (Part of Two County Trial), Sweden 1977   
Kopparberg (Part of Two County Trial), Sweden 1977   
Edinburgh, United Kingdom 1976 
The study design and conduct make these results difficult to assess or combine with the results of other trials.
NBSS-1, Canada 1980 
NBSS-2, Canada 1980 
Stockholm, Sweden 1981 
Gothenberg, Sweden 1982
Screening for breast cancer does not affect overall mortality, and the absolute benefit for breast cancer mortality appears to be small.
A way to view the potential benefit of breast cancer screening is to estimate the number of lives extended because of early breast cancer detection.   Harris  estimated the outcomes of 10,000 women aged 50 to 70 years who undergo a single screen. Mammograms will be normal (true negatives and false negatives) in 9,500 women. Of the 500 abnormal screens, between 466 and 479 will be false-positives, and 100 to 200 of these women will undergo invasive procedures. The remaining 21 to 34 abnormal screens will be true positives, indicating breast cancer. Some of these women will die of breast cancer in spite of mammographic detection and optimal therapy, and some may live long enough to die of other causes even if the cancer has not been screen detected. The number of extended lives attributable to mammographic detection is between two and six. Another expression of this analysis is that one life may be extended per 1,700 to 5,000 women screened and followed for 15 years. The same analysis for 10,000 women aged 40 to 49 years, assuming the same 500 abnormal examinations, results in an estimate that 488 of these will be false-positives, and 12 will be breast cancer. Of these 12, there will probably be only one to two lives extended. Thus, for women aged 40 to 49 years, it is estimated that one to two lives may be extended per 5,000 to 10,000 mammograms.
Population-Based Screening Programs, Including Studies of Effectiveness of Screening
Although the RCTs of screening have addressed the issue of the efficacy of screening (i.e., the extent to which screening reduces breast cancer mortality under the ideal conditions of an RCT), they do not provide information about the effectiveness of screening (i.e., the extent to which screening is reducing breast cancer mortality in the U.S. population). Studies that provide information on this issue include nonrandomized controlled studies of screened versus nonscreened populations, case-control studies of screening in real communities, and modeling studies that examine the impact of screening on large populations. An important issue in all of these studies is the extent to which they can control for additional effects on breast cancer mortality such as improved treatment and heightened awareness of breast cancer in the community.
Two population-based, observational studies from Sweden compared breast cancer mortality in the presence and absence of screening mammography programs. One study compared two adjacent time periods within 7 of the 25 counties in Sweden and concluded a statistically significant breast cancer mortality reduction of 18% to 32% due to screening.  The most important bias in this study is that the advent of screening in these counties occurred over a period during which dramatic improvements were being made in the effectiveness of adjuvant breast cancer therapy. The authors do not present data on treatment received, nor do they address differences in treatment that could at least partially explain the observed reduction in breast cancer mortality. The second study considered an 11-year period and compared seven counties that had screening programs with five counties that did not.  It concluded that there was a statistically nonsignificant reduction of 16% to 20% in favor of screening. The most important bias in this study was similar to that in the first study. The counties in the control group were rural. Those in the screening group included some urban areas and in general they were largely in the southern, more densely populated part of the country in comparison with the control counties. Participants were accrued over a 7-year period (about 1980–1987) during which effective adjuvant hormonal therapy and chemotherapy were being introduced. The authors do not address differences in treatment in the various geographic areas that could explain the observed reduction in breast cancer mortality.
In Nijmegen, the Netherlands, a population-based screening program was undertaken in 1975, and breast cancer mortality rates were compared with those in the neighboring town Arnhem and to all of the Netherlands. No difference in breast cancer mortality could be identified  despite the fact that case-cohort studies showed that screened women have decreased mortality. One such study was performed in Nijmegen itself, with an odds ratio of 0.48, for screened versus unscreened women.  Explanations for the lack of demonstrable benefit include earlier diagnosis of breast cancer in the general population (due to increased public awareness) and documented trends for the diagnosis of cancers with favorable prognostic indicators. Furthermore, adjuvant systemic therapy decreases breast cancer mortality, and its use may decrease the impact of early detection.
A community-based case-control study of screening as practiced in excellent U.S. health care systems between 1983 and 1998 found no association between previous screening and reduced breast cancer mortality. Mammography screening rates, however, were generally low. 
Since 1990, there has been a sustained reduction in age-adjusted breast cancer mortality in the United States of about 2% per year. Between 1990 and 2000, the cumulative reduction was 24%. To address the contribution of screening and adjuvant therapy to this decline, the National Cancer Institute formed a consortium of seven modeling groups.  These groups developed independent statistical models of female breast cancer incidence and breast cancer mortality in the United States. They used common inputs for the dissemination of screening mammography, chemotherapy, and hormonal therapy and for the benefits of treatment interventions. All seven models ascribed some benefit to both screening and adjuvant treatment, but their estimates of the relative and absolute contributions varied considerably. The estimated proportion of the total mortality reduction contributed by screening varied from 28% to 65%, with adjuvant treatment contributing the rest. The variability across models for the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty and higher complexity associated with estimating screening benefit.
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2. Gøtzsche PC, Nielsen M: Screening for breast cancer with mammography. Cochrane Database Syst Rev (4): CD001877, 2006.
3. Nyström L, Andersson I, Bjurstam N, et al.: Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 359 (9310): 909-19, 2002.
4. Shapiro S, Venet W, Strax P, et al.: Ten- to fourteen-year effect of screening on breast cancer mortality. J Natl Cancer Inst 69 (2): 349-55, 1982.
5. Shapiro S: Periodic screening for breast cancer: the Health Insurance Plan project and its sequelae, 1963-1986. Baltimore, Md: Johns Hopkins University Press, 1988.
6. Andersson I, Aspegren K, Janzon L, et al.: Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial. BMJ 297 (6654): 943-8, 1988.
7. Nyström L, Rutqvist LE, Wall S, et al.: Breast cancer screening with mammography: overview of Swedish randomised trials. Lancet 341 (8851): 973-8, 1993.
8. Tabár L, Fagerberg CJ, Gad A, et al.: Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare. Lancet 1 (8433): 829-32, 1985.
9. Tabàr L, Fagerberg G, Duffy SW, et al.: Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 30 (1): 187-210, 1992.
10. Tabar L, Fagerberg G, Duffy SW, et al.: The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit. J Epidemiol Community Health 43 (2): 107-14, 1989.
11. Gotzsche PC, Olsen O: Correspondence. Authors' reply. Lancet 355(9205): 752, 2000.
12. Roberts MM, Alexander FE, Anderson TJ, et al.: Edinburgh trial of screening for breast cancer: mortality at seven years. Lancet 335 (8684): 241-6, 1990.
13. Miller AB, To T, Baines CJ, et al.: The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med 137 (5 Part 1): 305-12, 2002.
14. Bailar JC 3rd, MacMahon B: Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion. CMAJ 156 (2): 193-9, 1997.
15. Baines CJ, Miller AB, Kopans DB, et al.: Canadian National Breast Screening Study: assessment of technical quality by external review. AJR Am J Roentgenol 155 (4): 743-7; discussion 748-9, 1990.
16. Fletcher SW, Black W, Harris R, et al.: Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 85 (20): 1644-56, 1993.
17. Miller AB, Baines CJ, To T, et al.: Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 147 (10): 1477-88, 1992.
18. Frisell J, Eklund G, Hellström L, et al.: Randomized study of mammography screening--preliminary report on mortality in the Stockholm trial. Breast Cancer Res Treat 18 (1): 49-56, 1991.
19. Kerlikowske K: Efficacy of screening mammography among women aged 40 to 49 years and 50 to 69 years: comparison of relative and absolute benefit. J Natl Cancer Inst Monogr (22): 79-86, 1997.
20. Glasziou PP, Woodward AJ, Mahon CM: Mammographic screening trials for women aged under 50. A quality assessment and meta-analysis. Med J Aust 162 (12): 625-9, 1995.
21. Harris R, Leininger L: Clinical strategies for breast cancer screening: weighing and using the evidence. Ann Intern Med 122 (7): 539-47, 1995.
22. Duffy SW, Tabár L, Chen HH, et al.: The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties. Cancer 95 (3): 458-69, 2002.
23. Jonsson H, Nyström L, Törnberg S, et al.: Service screening with mammography of women aged 50-69 years in Sweden: effects on mortality from breast cancer. J Med Screen 8 (3): 152-60, 2001.
24. Broeders MJ, Peer PG, Straatman H, et al.: Diverging breast cancer mortality rates in relation to screening? A comparison of Nijmegen to Arnhem and the Netherlands, 1969-1997. Int J Cancer 92 (2): 303-8, 2001.
25. Verbeek AL, Hendriks JH, Holland R, et al.: Reduction of breast cancer mortality through mass screening with modern mammography. First results of the Nijmegen project, 1975-1981. Lancet 1 (8388): 1222-4, 1984.
26. Elmore JG, Reisch LM, Barton MB, et al.: Efficacy of breast cancer screening in the community according to risk level. J Natl Cancer Inst 97 (14): 1035-43, 2005.
27. Berry DA, Cronin KA, Plevritis SK, et al.: Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353 (17): 1784-92, 2005.
Harms of Screening
Mammography screening may be effective in reducing breast cancer mortality in certain populations. As with any medical intervention, it has limitations, which can pose potential harm to women who participate. These limitations are best described as false-negatives (related to the sensitivity of the test), false-positives (related to the specificity), overdiagnosis (true positives that will not become clinically significant), and radiation risk.
The specificity of mammography (refer to the Mammography section) affects the number of “unnecessary” interventions due to false-positive results. Even though breast cancer is the most common noncutaneous cancer in women, only a very small fraction (0.1% to 0.5%, depending on age) actually have the disease when they are screened. Therefore, even though the specificity of mammography exceeds 90%, most abnormal tests are false-positives.  Women with abnormal screening test results have additional procedures performed to determine whether the mammographic finding is cancer. These procedures include additional mammographic imaging (e.g., magnification of the area of concern), ultrasound, and tissue sampling (by fine-needle aspiration, core biopsy, or excisional biopsy). A study of breast cancer screening in 2,400 women enrolled in a health maintenance organization found that over a 10-year period, 88 cancers were diagnosed, 58 of which were identified on mammography. During that period, one third of the women had an abnormal mammogram result that required additional testing, including 539 additional mammograms, 186 ultrasound examinations, and 188 biopsies. The actuarial cumulative biopsy rate (the rate of true positives) due to mammographic findings was approximately 1 in 4 (23.6%). The positive predictive value (PPV) of an abnormal screening mammogram in this population was 6.3% for women aged 40 to 49 years, 6.6% for women aged 50 to 59 years, and 7.8% for women aged 60 to 69 years.  A subsequent analysis and modeling of data from the same cohort of women, all of whom were continuously enrolled in the Harvard Pilgrim Health Care plan from July 1983 through June 1995, estimated that the risk of having at least one false-positive mammogram was 7.4% (95% confidence interval [CI], 6.4%–8.5%) at the first mammogram, 26.0% (95% CI, 24.0%–28.2%) by the fifth mammogram, and 43.1% (95% CI, 36.6%–53.6%) by the ninth mammogram.  Cumulative risk of at least one false-positive by the ninth mammogram varied from 5% to 100%, depending on four patient variables and three radiologic variables. Patient variables independently associated with increased chance of a false-positive result included younger age, higher number of previous breast biopsies, family history of breast cancer, and current estrogen use. Radiologic variables included longer time between screenings, failure to compare the current and previous mammograms, and the individual radiologist’s tendency to interpret mammograms as abnormal, which ranged from 2.6% to 24.4% across 93 radiologists in the study. Overall, the largest risk factor for having a false-positive mammogram was the individual radiologist’s tendency to read mammograms as abnormal. The authors noted that confidence intervals for estimates of false-positives beyond five mammograms were wide because of the relatively small numbers of women in the analysis with more than five mammograms.
By reviewing Medicare claims following mammographic screening in 23,172 women older than 65 years, one study  found that 85 per 1,000 had follow-up testing and 23 per 1,000 had biopsies. The cancer detection rate was 7 per 1,000, so the PPV for an abnormal mammogram was 8%. For women older than 70 years, the PPV was 14%. An audit of mammograms done in 1998 at a single institution revealed that 14.7% of examinations resulted in a recommendation for additional testing (Breast Imaging Reporting and Data System category 0), 1.8% resulted in a recommendation for biopsy (categories 4 and 5), and 5.7% resulted in a recommendation for short-term interval mammography (category 3). Cancer was diagnosed in 1 out of 30 of the cases referred for additional testing. 
False Sense of Security
The sensitivity of mammography (refer to the Mammography section) ranges from 70% to 90%, depending on a woman’s age and the density of her breasts, which is affected by her genetic predisposition, hormone status, and diet. Assuming an average sensitivity of 80%, mammograms will miss approximately 20% of the breast cancers that are present at the time of screening (false-negatives). If a woman does not seek medical attention for a breast symptom or if her physician is reluctant to evaluate that symptom because she has a “normal” mammogram, she may suffer adverse consequences. Whereas the medical community has been carefully educated that a negative diagnostic mammogram should not deter work-up of a palpable lump, the medical and lay communities should be made aware that a negative screening mammogram misses one in five cancers.
Because radiation exposure is a known risk factor for the development of breast cancer, it is ironic that ionizing radiation is our best screening tool. The major predictors of risk are young age at the time of radiation exposure and the radiation dose. For women older than 40 years, the benefits of annual mammograms may outweigh any potential risk of radiation exposure due to mammography.  It is speculated that certain subpopulations of women may have an inherited susceptibility to ionizing radiation damage,   but mammography has never been shown to be harmful in these, or any, subgroups. In the United States, the mean glandular dose for screening mammography is 1 mGy to 2 mGy (100–200 mrad) per view or 2 mGy to 4 mGy (200–400 mrad) per standard two-view exam.  
Because large numbers of women have false-positive tests, the issue of psychological distress—which may be provoked by the additional testing—has been studied. A telephone survey of 308 women performed 3 months after screening mammography revealed that about one-fourth of the 68 women with a “suspicious” result were still experiencing worry that affected their mood or functioning, even though subsequent testing had ruled out a cancer diagnosis.  Several studies,    however, show that the anxiety following evaluation of a false-positive test leads to increased participation in future screening examinations.
The purpose of screening for cancer is to detect cancer before it becomes symptomatic and to change the course of disease by treating the cancer early. Cancers do not progress at the same rate, however, and not all early-stage cancer treatment is successful.
Lesions exist that fulfill the histologic criteria of cancer but would neither progress nor become clinically apparent in a patient's lifetime. Data confirming this concept come from pathologic examination of normal breast tissue. An overview of seven autopsy studies documents a median prevalence of 1.3% for invasive breast cancer (range, 0%–1.8%) and 8.9% for ductal carcinoma in situ (range, 0%–14.7%).   Detection and treatment of these lesions constitute overdiagnosis and do not confer any benefit to the patient. It is currently impossible to distinguish with certainty the cancers that will progress from those that will not.
Therefore, one of the consequences of screening a population of women is the detection, in some women, of cancers that are destined to remain occult during their lifetimes. When these clinically insignificant cancers are detected, there is no benefit, yet these women will undergo treatments such as surgery, radiation therapy, hormonal therapy, and chemotherapy. It is difficult to determine the proportion of screen-detected cancers that fall into this category.
Population-based comparisons of breast cancer incidence before and after adoption of screening suggest that overdiagnosis is a substantial problem.      One might expect that screening will have identified cancers earlier and that a rise in incidence rates would be followed by a subsequent compensatory decline. This, however, has not been observed. Cancer incidence rates increase substantially in screened populations, without a compensatory drop in later years. For example, in Sweden, the age-specific incidence rates doubled between 1986 and 2002 for all age groups participating in screening.  Another study in 11 rural Swedish counties documented a persistent increase in breast cancer incidence following the advent of screening.  A population-based study from Norway and Sweden showed increases in invasive breast cancer incidence of 54% in Norway and 45% in Sweden in women aged 50 to 69 years, following the introduction of nationwide screening programs. No corresponding decline in incidence in women older than age 69 years was ever seen.  Similar findings suggestive of overdiagnosis have been reported from the United Kingdom  and the United States.   Approximations of the magnitude of the problem of overdiagnosis range from 10% to 30% of newly diagnosed breast cancer cases, depending on utilization and intensity of screening.  
1. Kerlikowske K, Grady D, Barclay J, et al.: Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 270 (20): 2444-50, 1993.
2. Elmore JG, Barton MB, Moceri VM, et al.: Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 338 (16): 1089-96, 1998.
3. Christiansen CL, Wang F, Barton MB, et al.: Predicting the cumulative risk of false-positive mammograms. J Natl Cancer Inst 92 (20): 1657-66, 2000.
4. Welch HG, Fisher ES: Diagnostic testing following screening mammography in the elderly. J Natl Cancer Inst 90 (18): 1389-92, 1998.
5. Rosen EL, Baker JA, Soo MS: Malignant lesions initially subjected to short-term mammographic follow-up. Radiology 223 (1): 221-8, 2002.
6. Feig SA, Ehrlich SM: Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits. Radiology 174 (3 Pt 1): 638-47, 1990.
7. Helzlsouer KJ, Harris EL, Parshad R, et al.: Familial clustering of breast cancer: possible interaction between DNA repair proficiency and radiation exposure in the development of breast cancer. Int J Cancer 64 (1): 14-7, 1995.
8. Swift M, Morrell D, Massey RB, et al.: Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325 (26): 1831-6, 1991.
9. Kopans DB: Mammography and radiation risk. In: Janower ML, Linton OW, eds.: Radiation Risk: a Primer. Reston, Va: American College of Radiology, 1996, pp 21-22.
10. Suleiman OH, Spelic DC, McCrohan JL, et al.: Mammography in the 1990s: the United States and Canada. Radiology 210 (2): 345-51, 1999.
11. Lerman C, Trock B, Rimer BK, et al.: Psychological side effects of breast cancer screening. Health Psychol 10 (4): 259-67, 1991.
12. Gram IT, Lund E, Slenker SE: Quality of life following a false positive mammogram. Br J Cancer 62 (6): 1018-22, 1990.
13. Burman ML, Taplin SH, Herta DF, et al.: Effect of false-positive mammograms on interval breast cancer screening in a health maintenance organization. Ann Intern Med 131 (1): 1-6, 1999.
14. Pisano ED, Earp J, Schell M, et al.: Screening behavior of women after a false-positive mammogram. Radiology 208 (1): 245-9, 1998.
15. Welch HG, Black WC: Using autopsy series to estimate the disease "reservoir" for ductal carcinoma in situ of the breast: how much more breast cancer can we find? Ann Intern Med 127 (11): 1023-8, 1997.
16. Black WC, Welch HG: Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med 328 (17): 1237-43, 1993.
17. Hemminki K, Rawal R, Bermejo JL: Mammographic screening is dramatically changing age-incidence data for breast cancer. J Clin Oncol 22 (22): 4652-3, 2004.
18. Jonsson H, Johansson R, Lenner P: Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden. Int J Cancer 117 (5): 842-7, 2005.
19. Johnson A, Shekhdar J: Breast cancer incidence: what do the figures mean? J Eval Clin Pract 11 (1): 27-31, 2005.
20. White E, Lee CY, Kristal AR: Evaluation of the increase in breast cancer incidence in relation to mammography use. J Natl Cancer Inst 82 (19): 1546-52, 1990.
21. Feuer EJ, Wun LM: How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach. Am J Epidemiol 136 (12): 1423-36, 1992.
22. Zahl PH, Strand BH, Maehlen J: Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 328 (7445): 921-4, 2004.
23. Gøtzsche PC, Nielsen M: Screening for breast cancer with mammography. Cochrane Database Syst Rev (4): CD001877, 2006.
24. Zackrisson S, Andersson I, Janzon L, et al.: Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study. BMJ 332 (7543): 689-92, 2006.
Women with Limited Life Expectancy
Achieving balance between the benefits and harms of screening is especially important for women with a life expectancy of no longer than 5 years. Such women might have end-stage renal disease, severe dementia, terminal cancer, or severe functional dependencies in activities of daily living. Early cancer detection and prompt treatment are unlikely to reduce morbidity or mortality within the woman's 5 years of expected survival, but the negative consequences of screening will occur immediately. Abnormal screening may trigger additional testing with attendant anxiety. In particular, the detection of low-risk malignancy would probably result in a recommendation for treatment, which could impair rather than improve quality of life, without improving survival. Despite these considerations, many women with poor life expectancy due to age or health status often undergo screening mammography. 
Screening mammography in women older than 65 years often results in additional diagnostic testing in 85 per 1,000, with cancer diagnosed in nine. The testing is often accomplished over many months, which may cause anxiety due to diagnostic uncertainty.  While screening mammography may yield cancer diagnoses in approximately 1% of elderly women, many of these cancers are low risk. A study of California Medicare beneficiaries aged 65 to 79 years demonstrated this clearly. The relative risk (RR) of detecting local breast cancer was 3.3 (95% confidence interval, 3.1–3.5) among screened women. Diagnosis of metastatic cancer was reduced among screened women (RR = 0.57), suggesting there may be benefit of mammography screening in elderly women, though it comes with an increased risk of overdiagnosis. 
One study examined the usefulness of mammography in evaluating breast complaints in 1,908 women aged 35 years or younger. Although 23 were found to have palpable cancers, none of the 1,908 mammograms contributed any information that affected patient management. 
Women with Thoracic Radiation
Screening has been recommended for women exposed to therapeutic radiation, especially if exposed at a young age. Screening mammography and magnetic resonance imaging can identify early-stage cancers, but the benefits and risks have not been clearly defined.
Although age-adjusted breast cancer incidence rates are higher in white women than in black women, mortality rates are higher in black women. Among breast cancer cases diagnosed from 1995 to 2001, 64% of white women and only 53% of black women had localized disease. The 5-year relative survival rate for localized disease was 98.5% for white women and 92.2% for black women; for regional disease, it was 82.9% for white women and 68.3% for black women; and for distant disease, it was 27.7% for white women and 16.3% for black women. Both breast cancer incidence and mortality are lower among Hispanic and Asian/Pacific Islander women than among white and black women. 
Several explanations for these findings have been proposed, including lower socioeconomic status, lower level of education, and less access to screening and treatment services. Population-based studies demonstrate that, compared with other groups, Medicaid recipients and uninsured patients of all races have later-stage breast cancer diagnosis, and survival from the time of diagnosis is shorter. This difference is associated with socioeconomic status and may reflect lack of participation in screening activities.   Black women older than 65 years are less likely to undergo mammogram screening. Among regular users of mammography, however, cancer was diagnosed in black and white women at similar stages. 
Similar studies of Hispanic populations have been done. Breast cancer stage at diagnosis in San Diego County was more advanced for Hispanic than for white women, especially for those younger than 50 years. Low-income whites were more likely to have late-stage diagnosis than high-income whites. Among Hispanic women, there was no difference according to income, but all the Hispanic groups were at or below the lowest white income level.  In New Mexico, a population-based case-control study examined reproductive histories of 719 Hispanic and 836 white breast cancer patients, with half of each group having breast cancer. The Hispanic women had higher body mass index, higher parity, and earlier pregnancies.  Whereas reproductive factors such as age at first full-term birth, parity, and duration of lactation accounted for some of the ethnic differences in postmenopausal women, there was no evidence that these factors played a role in the differences in premenopausal patients. A study of mammography screening in a health maintenance organization in Albuquerque found that Hispanic women had consistently lower rates of screening than whites (50.6% vs. 65.5% in 1989, and 62.7% vs. 71.6% in 1996).  Predictors of more advanced stage at diagnosis included Hispanic race (odds ratio, 2.12) and younger age.
Approximately 1% of all breast cancers occur in males. Most cases are diagnosed during the evaluation of palpable lesions and treatment consists of surgery, radiation, and systemic adjuvant hormone therapy or chemotherapy. There are no data on the benefits or risks of screening.
1. Walter LC, Lindquist K, Covinsky KE: Relationship between health status and use of screening mammography and Papanicolaou smears among women older than 70 years of age. Ann Intern Med 140 (9): 681-8, 2004.
2. Welch HG, Fisher ES: Diagnostic testing following screening mammography in the elderly. J Natl Cancer Inst 90 (18): 1389-92, 1998.
3. Smith-Bindman R, Kerlikowske K, Gebretsadik T, et al.: Is screening mammography effective in elderly women? Am J Med 108 (2): 112-9, 2000.
4. Hindle WH, Davis L, Wright D: Clinical value of mammography for symptomatic women 35 years of age and younger. Am J Obstet Gynecol 180 (6 Pt 1): 1484-90, 1999.
5. Ries LAG, Eisner MP, Kosary CL, et al., eds.: SEER Cancer Statistics Review, 1975-2002. Bethesda, Md: National Cancer Institute, 2005. Also available online. Last accessed May 30, 2008.
6. Roetzheim RG, Pal N, Tennant C, et al.: Effects of health insurance and race on early detection of cancer. J Natl Cancer Inst 91 (16): 1409-15, 1999.
7. Bradley CJ, Given CW, Roberts C: Race, socioeconomic status, and breast cancer treatment and survival. J Natl Cancer Inst 94 (7): 490-6, 2002.
8. McCarthy EP, Burns RB, Coughlin SS, et al.: Mammography use helps to explain differences in breast cancer stage at diagnosis between older black and white women. Ann Intern Med 128 (9): 729-36, 1998.
9. Bentley JR, Delfino RJ, Taylor TH, et al.: Differences in breast cancer stage at diagnosis between non-Hispanic white and Hispanic populations, San Diego County 1988-1993. Breast Cancer Res Treat 50 (1): 1-9, 1998.
10. Gilliland FD, Hunt WC, Baumgartner KB, et al.: Reproductive risk factors for breast cancer in Hispanic and non-Hispanic white women: the New Mexico Women's Health Study. Am J Epidemiol 148 (7): 683-92, 1998.
11. Frost FJ, Tollestrup K, Trinkaus KM, et al.: Mammography screening and breast cancer tumor size in female members of a managed care organization. Cancer Epidemiol Biomarkers Prev 7 (7): 585-9, 1998.
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Changes to This Summary (06/18/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Breast Cancer Screening Modalities
Added text to state that studies have shown relatively little impact of false-positive test results on the use of subsequent mammography screening behavior, but false-positive test results may have long-term consequences, such as anxiety about breast cancer (cited Brewer et al. as reference 33).
Added text to state that there is increasing interest in using breast MRI as a screening test for breast cancer among women at elevated risk of breast cancer based on BRCA1/2 mutation carriers, a strong family history of breast cancer, or several genetic syndromes such as Li-Fraumeni or Cowden disease, and that breast MRI is a more sensitive, but less specific, modality for breast cancer detection compared with screening mammography (cited Lord et al. as reference 64 and Lehman et al. as reference 65).
Added text to state that direct back-to-back comparisons of breast MRI and mammography in young high-risk women report MRI sensitivities ranging from 71% to 100% versus mammography sensitivities of 20% to 50%.
Added text to state that it is unknown whether the increase in cancer detection is worthwhile, given the large increase in false-positive rates (cited Bermejo-Pérez et al. as reference 68).
Added text to state that the clinical role of MRI in breast imaging for average-risk women is still reserved for diagnostic evaluation.
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Additional PDQ Summaries
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Date last modified 2008-06-18