David Cohen, M.D.·Published 11 June 2008·12 min read
Key points
By convention, in the United States, most guidelines for breast cancer screening recommend that women begin screening at age 40 or at some time in their 40s.
Smith: Cancer Screening, Department of Cancer Control, American Cancer Society, Atlanta, Georgia C.
Since 1997, the ACS, NCI, and ACR have released updated guidelines for breast cancer screening, in large part informed by new data published in 1997.
The NCI guidelines also recommend screening at intervals of 1 to 2 years versus annual screening and encourage women at higher risk to consult with their physicians about establishing an interval for periodic screening that is appropriate in their individual case.
By convention, in the United States, most guidelines for breast cancer screening recommend that women begin screening at age 40 or at some time in their 40s. Guidelines that recommend screening beginning at age 50 are based more on previous debates over efficacy of screening before age 50 than on disease burden. The age of 40 is admittedly arbitrary and based on the legacy of methodologic decisions related to choosing study populations for the trials. Shapiro and colleagues included women age 40 and older after they observed that more than one-third of the premature mortality from breast cancer occurred in women diagnosed between the ages of 40 and 49.
Since 1997, the ACS, NCI, and ACR have released updated guidelines for breast cancer screening, in large part informed by new data published in 1997. Each organization recommends that women begin regular screening mammography in their 40s. The United States Preventive Services Task Force currently recommends mammography every 1 to 2 years for women beginning at age 50, having concluded that there is insufficient evidence to recommend for or against breast cancer screening before the age of 50. However, their last guidelines update was published in 1996, before the availability of more recent individual trial and meta-analysis findings. NCI recommendations differ from those of the ACS and ACR by not specifying a specific age to begin screening.
The NCI guidelines also recommend screening at intervals of 1 to 2 years versus annual screening and encourage women at higher risk to consult with their physicians about establishing an interval for periodic screening that is appropriate in their individual case. Current differences in breast cancer screening guidelines are a function of the timing of evidence-based literature reviews and different approaches to evidence-based medicine.
Some have questioned the value of screening women older than age 70, based on both lack of evidence from randomized trials (only one trial included women over the age of 70) and lower cost-effectiveness. On the issue of a lack of data, the U.S. Preventive Services Task Force found little evidence to conclude that breast cancer screening would be any less beneficial in women older than age 70.
Further, although comorbidity increases with increasing age, a significant percentage (71%) of the population older than age 65 rate their health as excellent, very good, or good. Given the high breast cancer incidence and mortality among women older than age 65, it is a mistake to presume that screening is not beneficial to this group. The ACS has asserted that there is no upper age limit for screening mammography, and as a general rule as long as a woman is in reasonably good health and does not have such significant comorbidity that she would not be a candidate for surgery, screening is recommended.
Whereas some organizations recommend breast self-examination (BSE) and CBE in their guidelines, others do not, mostly because of the lack of clear evidence of their efficacy as a stand-alone examination or in combination with mammography. Randomized trials of screening have shown mortality reductions among women invited to screening that included either mammography or mammography in combination with CBE. In the HIP study and the BCDDP, CBE was responsible for finding some cancers not detected by mammography.
Written and revised by
David Cohen, M.D.
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However, it is unclear what CBE contributes to breast cancer detection apart from mammography, although few would question the value of CBE as a complementary modality. Some breast cancers cannot be seen on a mammogram, or the mammographic examination may be enhanced if there is awareness of a palpable mass detected by CBE. For this reason, the ACS has recommended that CBE should occur close to and before the occasion of a screening mammogram. Furthermore, recommendations from the AHCPR's Quality Determinants of Mammography strongly assert that a negative mammogram in the presence of a palpable mass does not rule out breast cancer. It should be stressed, however, that the value of CBE is determined by the quality of the examination. {pagebreak}
The value of BSE is similar to that of CBE - that is, it is a form of low-cost surveillance for breast changes that should be brought to the attention of a physician. For women younger than age 40 who are at average risk, routine BSE can heighten awareness of the normal composition of the breasts. This benefit continues after a woman begins undergoing routine mammography, although the greater advantage is the potential to be alert to a palpable mass that may have been missed by recent mammography or a lesion that is fast growing. One methodologic problem associated with the evaluation of BSE relates to whether self-detected tumors are found during BSE or at some other time. However, the more important issue is awareness of an abnormality rather than the occasion of detection (i.e., self-discovery versus BSE).
It is doubtful that new studies will provide additional insights into the value of these examinations; for this reason, the most pragmatic approach is to view these physical examinations in the context of their age-specific relevance. For women younger than age 40, when breast cancer incidence is comparatively lower, regular BSE and periodic CBE provide an opportunity to identify the emergence of a palpable mass earlier rather than later. After a woman begins having regular mammograms, CBE and BSE provide a safeguard against the limitations of mammography.
Mammography participation rates rose rapidly in the late 1980s and have continued to increase during the last decade. Among states (n = 50, plus the District of Columbia) participating in the CDC's Behavioral Risk Factor Surveillance System, the median percentage of women age 40 and older who reported ever having had a mammogram is 84% (range, 71.8 to 91.4). The median percentage of women reporting a recent mammogram is lower and declines with increasing age. Among women aged 40 to 49, the median percentage reporting a mammogram in the past 2 years is 65.4% (range, 50.2 to 74.4). Although not directly comparable, the median proportion of women aged 50 and older who reported having had a mammogram in the past year is 57% (range, 41.8 to 70.1), and for women 65 and older, the median proportion is 54.1% (range, 38.3 to 67.7).
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As noted previously in the section Principles of Cancer Screening, an important factor in planning a screening program is identifying a population with sufficient prevalence of occult disease. It would seem logical, then, that breast cancer risk factors other than age might prove useful in improving the efficiency of screening programs. This potential could extend to determining when to begin screening, which women should be screened at shorter or wider screening intervals, and, ideally, organizing screening programs on the basis of risk so that a truly low-risk population could be excluded from routine testing.
What, then, is the potential for making individual decisions about screening based on risk apart from the recommendations or guidelines issued by medical organizations? When answering these questions, it is important to distinguish between program considerations relating to cost-effectiveness and the decision reached by an individual woman based on her unique circumstances.
For women at very high risk, due to a significant family history in first-degree relatives diagnosed premenopausally, a family history suggestive of an inherited predisposition to breast cancer, or confirmation of an inherited mutation of known significance on a breast cancer susceptibility gene, more aggressive surveillance has been recommended based on expert opinion. Women with a prior diagnosis of breast cancer, DCIS, lobular neoplasia, or atypical hyperplasia might also reach a decision with their physician to establish a program of more aggressive surveillance.
For women who do not fall into these higher-risk categories, it also has been proposed that informed decisions about screening should be made weighing comparative risks (e.g., cost, inconvenience, anxiety associated with false-positive results, harm associated with avoidable biopsy) and benefits. The underlying message in this recommendation is that women should understand their risk of breast cancer, the benefit of screening, and the comparative risk of harm associated with screening. {pagebreak}
Because the majority of women are not diagnosed with breast cancer in their lifetimes, they could choose to not be screened, be screened less often, or delay screening in order to reduce their higher risk of a false-positive examination compared with a lower likelihood of being diagnosed with breast cancer. It is not an entirely unreasonable recommendation, provided that women fully understand the issues and implications of their choices and the fact that third-party payers do not make these choices for them. Further, individuals vary in the degree to which they wish to make individual decisions about screening and in the degree to which various methods of information delivery and kinds of information fully communicate the issues in a manner that ensures complete understanding. In other words, we face an immense challenge in assisting those women who wish to make informed decisions about screening to do so.
Because breast cancer risk increases with increasing age, concerns about comparative risks and benefits associated with breast cancer screening have been raised. At an age when breast cancer risk is comparatively low, Gail and Rimer have proposed that a woman's risk factor profile could be used to make decisions about whether to begin screening before age 50.
Their model, which is derived from BCDDP data, is based on the assumption that regular mammographic screening is justified for a 50-year-old woman with none of the important risk factors. Regular screening would be justified for women in their 40s if they have a prior history of breast cancer; atypical hyperplasia on a previous breast biopsy; two or more breast biopsies even with benign results; a known mutation on a breast cancer susceptibility gene; a mother, sister, or daughter previously diagnosed with breast cancer; or if they are age 45 to 49 with at least 75% breast density. For women in their 40s who do not fall into any of these categories, age at menarche, number of previous breast biopsies, and age at first live birth would be the basis for an informed decision about screening.
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For example, according to the authors, in a woman in her early 40s with no history of breast biopsies and age at first live birth younger than 30 years, delay would be an option. Based on their estimates, only approximately 10% of 40-year-old women would make a decision to be screened if this model were followed, compared with 68% by age 45 and 95% by age 49. Because breast cancer risk increases with increasing age, their model may prove useful for women who wish to make an informed, risk-based decision about when to begin screening. No data are included with this model to estimate the proportion of incident cases within specific ages that would be identified if all women followed this approach. Although this kind of information is more immediately relevant for program planning, it is unknown whether it would be useful for making an informed decision at the individual level.
Another tool available to help women understand their individual risk is an interactive computer program for breast cancer risk assessment that has come to be known as the risk disk. This risk assessment tool is available from NCI and was developed to determine eligibility for participation in the Breast Cancer Prevention Trial. This program cannot estimate risk for women with a prior history of breast ancer, a history of DCIS or lobular neoplasia, or an inherited mutation on a known breast cancer susceptibility gene.
However, for women who do not fall into these higher-risk categories, absolute risk can be estimated for the next 5 years or to age 90, compared with a woman with no risk factors, based on current age, age at menarche, age at first live birth, and number of offspring; family history of breast cancer in first-degree relatives; and history of breast biopsy, including the presence of atypical hyperplasia. It is important to keep in mind that the comparison group with no risk factors does not represent an average woman. This woman's risk to age 90 is 6.7%, whereas an average woman's risk is closer to 9%.
These tools may have their greatest value in helping women understand individual risk against the backdrop of health education messages and articles in the popular press that emphasize risk as a basis for raising awareness about breast cancer prevention and early detection. Although well intentioned, there is concern that these messages have heightened anxiety far past the point at which they become sufficiently motivational at the individual level.{pagebreak}
Are risk factors other than age useful for establishing screening intervals? No study has shown an association between a breast cancer risk factor and the length of the detectable preclinical phase. Thus, any attempt to decide on the basis of risk factors whether to be screened more or less frequently than recommended guidelines would be a decision based on the underlying probability of disease, not the underlying probability of having a longer or shorter sojourn time. It may also be a decision based on one's concern about the risk of an abnormal mammogram and potential interventions that ultimately may be false-positives.
In this case, less frequent screening may reduce the risk of an avoidable intervention based on a false-positive result simply based on exposure to screening. However, that might not prove true, because specificity tends to be lower at the prevalent screen, and therefore it is by no means certain that less frequent screening reduces the odds of false-positive results. Here again, a woman would need to reconcile the greater odds of a false-positive examination compared with the lower odds of developing breast cancer and consider the relative benefits and potential costs associated with her decision.
On a population basis, risk-based screening for breast cancer has never been shown to have much potential to identify the majority of new cases by screening a subgroup of women at higher risk. In 1984, Solin et al. reported on the screening experience of 17,543 women, for whom data on eight risk factors were collected (including any family history, prior breast biopsy, menstrual history, pregnancy history, lactation, and hormone use). They concluded that more than one-half of the 246 cases diagnosed would not have been detected if the program had only screened women with either prior breast biopsy or family history and that more than 40% would have been missed if the program had been limited to any one of the listed risk factors.
In 1987, Alexander and colleagues reported similar findings from the analysis of Edinburgh trial data; by screening the 20% of the population at higher risk due to having had a prior biopsy or a family history in a mother or sister, only 30% of the first-round cancers would have been detected. When menopausal status or nulliparity/first birth after age 30 were included, the proportion of new cases that would have been detected in the first round increased to 29.6%. Again, concentrating on the more important risk factors would fail to identify the majority of prevalent cancers in an asymptomatic population.
Madigan et al. recently reported population-attributable risk estimates for breast cancer using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study. Using well-established risk factors, such as later age at first live birth, nulliparity, higher family income, and family history of breast cancer in first-degree relatives, these risk factors were associated with approximately 41% of breast cancer cases in the United States In each of these instances, it is estimated that fewer than one-half of breast cancer cases would be identified by a risk-based screening strategy applying well-established risk factors.
Robert A. Smith and Carl J. D'Orsi
R. A. Smith: Cancer Screening, Department of Cancer Control, American Cancer Society, Atlanta, Georgia C. J. D'Orsi: Diagnostic Radiology, University of Massachusetts Memorial Medical Center, Worchester, Massachusetts
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