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Brief Summary


GUIDELINE TITLE

   Screening for breast cancer: recommendations and rationale.

BIBLIOGRAPHIC SOURCE(S)

U.S. Preventive Services Task Force. Screening for breast cancer: recommendations and rationale. Ann Intern Med 2002

GUIDELINE STATUS

This is the current release of the guideline.

This release updates a previously published guideline: U.S. Preventive Services Task Force. Screening for breast cancer. In: Guide to clinical preventive services. 2nd ed. Baltimore (MD): Williams & Wilkins; 1996.

 

RECOMMENDATIONS



MAJOR RECOMMENDATIONS

Note from the National Guideline Clearinghouse and the U.S. Preventive Services Task Force: These recommendations were first released in February, 2002. Subsequent to their release, a 2002 publication provided additional data on outcomes and methods of four mammography trials conducted in Sweden. The additional followup data have been incorporated into the numeric estimates of effectiveness of mammography (see the "Potential Benefit" field), which differ minimally from those cited in the February 2002 release. Overall ratings of study quality were not affected. The recommendations remain unchanged.

The U.S. Preventive Services Task Force grades its recommendations (A, B, C, D, or I) and the quality of the overall evidence for a service (good, fair, poor). The definitions of these grades can be found at the end of the "Major Recommendations" field.

  • The U.S. Preventive Services Task Force recommends screening mammography, with or without clinical breast examination, every 1-2 years for women aged 40 and older. B recommendation

The U.S. Preventive Services Task Force found fair evidence that mammography screening every 12-33 months significantly reduces mortality from breast cancer. Evidence is strongest for women aged 50-69, the age group generally included in screening trials. For women aged 40-49, the evidence that screening mammography reduces mortality from breast cancer is weaker, and the absolute benefit of mammography is smaller, than it is for older women. Most, but not all, studies indicate a mortality benefit for women undergoing mammography at ages 40-49, but the delay in observed benefit in women younger than 50 makes it difficult to determine the incremental benefit of beginning screening at age 40 rather than at age 50. The absolute benefit is smaller because the incidence of breast cancer is lower among women in their 40s than it is among older women.

The U.S. Preventive Services Task Force concluded that the evidence is also generalizable to women aged 70 and older (who face a higher absolute risk of breast cancer) if their life expectancy is not compromised by comorbid disease. The absolute probability of benefits of regular mammography increase along a continuum with age, whereas the likelihood of harms from screening (false-positive results and unnecessary anxiety, biopsies, and cost) diminish from ages 40-70.

The balance of benefits and potential harms, therefore, grows more favorable as women age. The precise age at which the potential benefits of mammography justify the possible harms is a subjective choice. The U.S. Preventive Services Task Force did not find sufficient evidence to specify the optimal screening interval for women aged 40-49 (see the Clinical Considerations section below).

  • The U.S. Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine clinical breast examination (CBE) alone to screen for breast cancer. I recommendation

No screening trial has examined the benefits of clinical breast examination alone (without accompanying mammography) compared to no screening, and design characteristics limit the generalizability of studies that have examined clinical breast examination. The U.S. Preventive Services Task Force could not determine the benefits of clinical breast examination alone or the incremental benefit of adding clinical breast examination to mammography. The U.S. Preventive Services Task Force therefore could not determine whether potential benefits of routine clinical breast examination outweigh the potential harms.

  • The U.S. Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination (BSE). I recommendation

The U.S. Preventive Services Task Force found poor evidence to determine whether breast self-examination reduces breast cancer mortality. The U.S. Preventive Services Task Force found fair evidence that breast self-examination is associated with an increased risk of false-positive results and biopsies. Due to design limitations of published and ongoing studies of breast self-examination, the U.S. Preventive Services Task Force could not determine the balance of benefits and potential harms of breast self-examination.

Clinical Considerations

  • The precise age at which the benefits from screening mammography justify the potential harms is a subjective judgment and should take into account patient preferences. Clinicians should inform women about the potential benefits (reduced chance of dying from breast cancer), potential harms (e.g., false-positive results, unnecessary biopsies), and limitations of the test that apply to women their age. Clinicians should tell women that the balance of benefits and potential harms of mammography improves with increasing age for women between the ages of 40 and 70.
  • Women who are at increased risk for breast cancer (e.g., those with a family history of breast cancer in a mother or sister, a previous breast biopsy revealing atypical hyperplasia, or first childbirth after age 30) are more likely to benefit from regular mammography than women at lower risk. The recommendation for women to begin routine screening in their 40s is strengthened by a family history of breast cancer having been diagnosed before menopause.
  • The U.S. Preventive Services Task Force did not examine whether women should be screened for genetic mutations (e.g., BRCA1 and BRCA2) that increase the risk of developing breast cancer, or whether women with genetic mutations might benefit from earlier or more frequent screening for breast cancer.
  • In the trials that demonstrated the effectiveness of mammography in lowering breast cancer mortality, screening was performed every 12-33 months. For women aged 50 and older, there is little evidence to suggest that annual mammography is more effective than mammography done every other year. For women aged 40-49, available trials also have not reported a clear advantage of annual mammography over biennial mammography. Nevertheless, some experts recommend annual mammography based on the lower sensitivity of the test and on evidence that tumors grow more rapidly in this age group.
  • The precise age at which to discontinue screening mammography is uncertain. Only two randomized controlled trials enrolled women older than 69, and no trials enrolled women older than 74. Older women face a higher probability of developing and dying from breast cancer but also have a greater chance of dying from other causes. Women with comorbid conditions that limit their life expectancy are unlikely to benefit from screening.
  • Clinicians should refer patients to mammography screening centers with proper accreditation and quality assurance standards to ensure accurate imaging and radiographic interpretation. Clinicians should adopt office systems to ensure timely and adequate follow-up of abnormal results. A listing of accredited facilities is available at the U.S. Food and Drug Administration (FDA) Web site.
  • Clinicians who advise women to perform breast self-examination or who perform routine clinical breast examination to screen for breast cancer should understand that there is currently insufficient evidence to determine whether these practices affect breast cancer mortality, and that they are likely to increase the incidence of clinical assessments and biopsies.

Definitions:

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, or I), reflecting the strength of evidence and magnitude of net benefit (benefits minus harms).

A

The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians provide [the service] to eligible patients. (The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.)

B

The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians provide [the service] to eligible patients. (The USPSTF found at least fair evidence that [the service] improves health outcomes and concludes that benefits outweigh harms.)

C

The U.S. Preventive Services Task Force (USPSTF) makes no recommendation for or against routine provision of [the service]. (The US Preventive Services Task Force found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms it too close to justify a general recommendation.)

D

The U.S. Preventive Services Task Force (USPSTF) recommends against routinely providing [the service] to asymptomatic patients. (The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.)

I

The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. (Evidence that [the service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.)

The U.S. Preventive Services Task Force (USPSTF) grades the quality of the overall evidence for a service on a 3-point scale (good, fair, or poor).

Good

Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.

Fair

Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of evidence on health outcomes.

Poor

Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

CLINICAL ALGORITHM(S)

None provided

 

EVIDENCE SUPPORTING THE RECOMMENDATIONS



TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence supporting each recommendation is identified in the "Major Recommendations" field.

BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS



POTENTIAL BENEFITS

Effectiveness of Early Detection

Mammography

The U.S. Preventive Services Task Force (USPSTF) reviewed 8 randomized controlled trials (RCTs) of mammography (4 of mammography alone and 4 of mammography plus clinical breast examination) that have reported results with 11-20 years of follow-up. The U.S. Preventive Services Task Force found important methodological limitations in each trial, but rated only one trial as "poor" based on established criteria used by the U.S. Preventive Services Task Force to evaluate the quality of evidence for screening tests. The most serious problems concerned the assembly and maintenance of comparable groups, methods for ascertaining outcomes, and generalizability to routine practice. The U.S. Preventive Services Task Force concluded that the flaws were problematic but unlikely to negate the reasonably consistent and significant mortality reductions observed in these trials.

Imperfections in these mammography trials have been recognized and discussed in the literature and by the original investigators for many years. Recently, a 2001 Cochrane Collaboration review of the same trials concluded that six of the eight trials were "flawed" or of "poor quality" and that the pooled results from the remaining two better trials did not support a benefit from mammography. Although the U.S. Preventive Services Task Force was concerned about many (but not all) of the flaws identified in this review, it did not consider the presence of flaws sufficient reason in itself for rejecting trial results. Instead, it examined whether observed mortality reductions in the trials were likely to be explained by the biases potentially introduced by such flaws. Studies rated to be of "fair" quality by the U.S. Preventive Services Task Force contained flaws that were considered unlikely to account for observed benefits (or lack of benefits).

The trials reported mortality reductions ranging from no significant effect to a 32 percent reduction in breast cancer mortality. The meta-analysis performed for the U.S. Preventive Services Task Force on the most current published data found that the pooled effect size of the combined trials was sizable and statistically significant. After excluding data from one trial rated as poor quality by the U.S. Preventive Services Task Force, the summary relative risk (RR) of breast cancer death among women of all ages randomized to screening in the remaining seven trials was 0.84 (95 percent confidence interval [CI], 0.77 - 0.91).

Earlier subgroup analyses from mammography trials raised questions about whether screening is effective in women younger than 50. Seven trials enrolled women aged 40-49. Six of these were rated by the U.S. Preventive Services Task Force to be of at least "fair" quality, but only one of these was designed to specifically address the benefits of screening in this age group: it reported no reduction in breast cancer mortality with annual mammography and clinical breast examination. Of the remaining five fair-quality trials that included women younger than 50, one trial has reported significant mortality reduction with screening in this age group, three have reported non-significant mortality reductions, and one found no benefit. In a meta-analysis performed for the U.S. Preventive Services Task Force pooling results for women aged 40-49 in the six fair-quality trials, the summary relative risk of breast cancer mortality was 0.85 (95 percent CI 0.73-0.99) among screened women after 13 years of observation. These results are similar to prior meta-analyses based on older data.

Because these data represent a subgroup analysis of trials not designed to test the benefits of beginning screening at a specific age, questions remain about the additional benefits of beginning screening before age 50. On average, the time until mortality benefits begin to be observed in these trials is longer in women younger than 50 than in older women (8 years versus 4 to 6 years) and some of the observed benefits could be due to screening after age 50. Analyses of individual studies suggest that at least some of the mortality reduction is due to early detection of tumors before age 50, but definitive estimates of the proportion of benefits due to early screening cannot be made.

Clinical Breast Examination

No study has compared clinical breast examination to no screening. The reductions in breast cancer mortality in studies using mammography alone are comparable to those using mammography plus clinical breast examination.

Breast Self-examination

The role of breast self-examination in reducing breast cancer mortality has been evaluated in one Chinese and one Russian randomized controlled trial and one non-randomized controlled trial of breast self-examination education in the United Kingdom. None of the three trials has demonstrated a reduction in breast cancer mortality or significant improvements in the number or stage of cancers detected, with follow-up ranging from 5 to 14 years; follow-up is continuing in one trial that observed a slight non-significant reduction in mortality in the breast self-examination group at 9 years. In a good-quality nested case-control analysis from a Canadian screening study, the overall practice of breast self-examination was not associated with a reduction in mortality.

Although none of these studies provides support for breast self-examination, the U.S. Preventive Services Task Force concluded that these studies did not exclude a possible benefit, due to their limited duration of follow-up and questions about whether results from other countries are generalizable to women in North America.

Subgroups Most Likely to Benefit:

Mammography

Women who are at increased risk for breast cancer (e.g., those with a family history of breast cancer in a mother or sister, a previous breast biopsy revealing atypical hyperplasia, or first childbirth after age 30) are more likely to benefit from regular mammography than women at lower risk. The recommendation for women to begin routine screening in their 40s is strengthened by a family history of breast cancer having been diagnosed before menopause.

POTENTIAL HARMS

Potential Harms of Screening

Similar to other cancer screening tests, the large majority (80% to 90%) of abnormal screening mammograms or clinical breast examinations are false-positives. These may require follow-up testing or invasive procedures such as breast biopsy to resolve the diagnosis, and can result in anxiety, inconvenience, discomfort, and additional medical expenses. In one large community study, 6.5% of screening mammograms required some additional follow-up and, over a 10-year period, 23% of all women had experienced at least one abnormal mammogram. The cumulative risk of a false-positive result after 10 mammograms was estimated to be 49%. The proportion of false-positive results that lead to biopsy varies substantially in different settings. In screening trials, 1% to 6% of all women screened underwent biopsy, and the proportion of biopsies that revealed cancer ranged from 12% to 78%. In two randomized controlled trials, breast self-examination education resulted in a nearly two-fold increase in false-positive results, physician visits, and biopsies for benign disease.

The consequences of false-positive mammograms are uncertain. Most, but not all, studies report increased anxiety from an abnormal mammogram. At the same time, some studies report that women in the United States may be willing to accept a relatively high number of false-positive results in the population in return for the benefits of mammography. Studies do not indicate that false-positive results diminish adherence to subsequent screening.

False-negatives also occur with mammograms and clinical breast examination. Although false-negative results might provide false reassurance, the U.S. Preventive Services Task Force (USPSTF) found no data indicating these led to further delays in diagnosis.

Some experts view the over-diagnosis and treatment of ductal carcinoma in situ (DCIS) as a potential adverse consequence of mammography. Although the natural history of ductal carcinoma in situ is variable, many women in the United States are treated aggressively with mastectomy or lumpectomy and radiation. Given the dramatic increase in the incidence of ductal carcinoma in situ in the past two decades (750 percent) and autopsy series suggesting that there is a significant pool of ductal carcinoma in situ among women who die of other causes, screening may be increasing the number of women undergoing treatment for lesions that might not pose a threat to their health.

A final potential concern about mammography is radiation-induced breast cancer, but there are few data to directly assess this risk. A 1997 review, using risk estimates provided by the Biological Effects of Ionizing Radiation report of the National Academy of Sciences, estimated that annual mammography of 100,000 women for 10 consecutive years beginning at age 40 would result in up to 8 radiation-induced breast cancer deaths.

 

QUALITY STATEMENTS



QUALIFYING STATEMENTS

The U.S. Preventive Services Task Force did not review evidence regarding genetic screening, surveillance of women with prior breast cancer, or formal evaluation of new screening modalities that have not been studied in the general population.