Context Breast cancer screening in community practices may be different from
that in randomized controlled trials. New screening modalities are becoming
available.
Objectives To review breast cancer screening, especially in the community and to
examine evidence about new screening modalities.
Data Sources and Study Selection English-language articles of randomized controlled trials assessing
effectiveness of breast cancer screening were reviewed, as well as meta-analyses,
systematic reviews, studies of breast cancer screening in the community, and
guidelines. Also, studies of newer screening modalities were assessed.
Data Synthesis All major US medical organizations recommend screening mammography for
women aged 40 years and older. Screening mammography reduces breast cancer
mortality by about 20% to 35% in women aged 50 to 69 years and slightly less
in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of
women with abnormalities on screening mammograms do not have breast cancer
with variability based on such factors as age of the woman and assessment
category assigned by the radiologist. Studies comparing full-field digital
mammography to screen film have not shown statistically significant differences
in cancer detection while the impact on recall rates (percentage of screening
mammograms considered to have positive results) was unclear. One study suggested
that computer-aided detection increases cancer detection rates and recall
rates while a second larger study did not find any significant differences.
Screening clinical breast examination detects some cancers missed by mammography,
but the sensitivity reported in the community is lower (28% to 36%) than in
randomized trials (about 54%). Breast self-examination has not been shown
to be effective in reducing breast cancer mortality, but it does increase
the number of breast biopsies performed because of false-positives. Magnetic
resonance imaging and ultrasound are being studied for screening women at
high risk for breast cancer but are not recommended for screening the general
population. Sensitivity of magnetic resonance imaging in high-risk women has
been found to be much higher than that of mammography but specificity is generally
lower. Effect of the magnetic resonance imaging on breast cancer mortality
is not known. A balanced discussion of possible benefits and harms of screening
should be undertaken with each woman.
Conclusions In the community, mammography remains the main screening tool while
the effectiveness of clinical breast examination and self-examination are
less. New screening modalities are unlikely to replace mammography in the
near future for screening the general population.
Breast cancer screening, especially with mammography, has been recommended
for many decades,1 and the majority of women
older than 40 years in the United States participate in screening activities.2,3 Meanwhile, new screening modalities
have been introduced, and some of these have been increasingly incorporated
into community practice. However, none of the new technologies has been evaluated
for its effect on breast cancer mortality.
Community practice of screening may differ from the care provided within
randomized clinical trials and is less often discussed in review articles. Quiz Ref IDReviews of breast cancer screening usually emphasize efficacy and
results of randomized trials, particularly those involving screen-film mammography.4-7Efficacy of a screening tool is measured in experimental
studies under ideal circumstances.8 In contrast, effectiveness is defined as the extent to which a specific
intervention “when deployed in the field in routine circumstances, does
what it is intended to do for a specific population.”8
We systematically reviewed what is known about the community practice
of mammography, clinical breast examination, and breast self-examination,
when possible, comparing the results from community studies with those of
randomized clinical trials. In addition, we reviewed what is known about newer
screening modalities, specifically digital mammography, computer-aided detection
programs for mammography, ultrasound, and magnetic resonance imaging (MRI).
The evaluation of screening modalities, especially in the community
setting, is challenging for methodological, clinical, and ethical reasons.
Randomized clinical trials are considered the gold standard for evaluating
a new screening test. The long-term breast cancer mortality rate of women
randomized to receive a new screening test is compared with that of women
randomized to receive standard care. However, such trials are difficult to
conduct. They require tens of thousands of women who need to be followed up
for more than 15 years. Furthermore, because mammography screening has been
shown to be effective in some trials, it would likely be even more difficult
to demonstrate any additional efficacy of new tests. Finally, as treatment
for breast cancer has improved over time,9-11 the
impact of screening on breast cancer mortality may be increasingly difficult
to establish.
Because of these challenges, new screening tests are often first studied
by establishing characteristics of the tests themselves, rather than by studying
their effect on patient outcome such as breast cancer mortality. Important
test characteristics include sensitivity, specificity, safety, cost, simplicity,
and patient and clinician acceptability. We review what test characteristics
have been studied and the findings for each new modality. We also indicate
the study design and the end points studied for each screening test. Although
it is important to use resources wisely when considering a screening test
for a large segment of the population, cost-effectiveness analyses are not
reviewed.
Quiz Ref IDIt is important to determine the characteristics of
a screening test in a community setting if the test is to be used in that
setting. However, test characteristics of new modalities are usually evaluated
among women for whom the rate of breast cancer is higher than average, such
as women at increased risk of breast cancer or women in a diagnostic setting
with breast symptoms or known breast abnormalities. The reported sensitivity
and specificity of a test in these high-risk women may be different from the
sensitivity and specificity of the same test used in a general screening population.12 We therefore indicate if a test has been evaluated
as a diagnostic or screening test and if as a screening test, whether it has
been evaluated in women thought to be at increased risk or in the general
population.
For this review, searches of MEDLINE, The Cochrane Library, the National
Guideline Clearinghouse Web site, the US Preventive Services Task Force recommendations
and reviews,5,13 and the International
Agency for Research on Cancer Handbook of Cancer Prevention (IARC)4 were performed to identify English-language articles
about breast cancer screening. Examples of search terms included mass screeningandbreast and then the specific modality (eg, mammography, breast examination, digital
mammography, computer assisted diagnosis or computer aided detection, magnetic resonance
imaging, ultrasound or ultrasonography). The bibliographies of retrieved articles were also
scanned to retrieve additional relevant articles. Details regarding search
terms are available from the authors.
Eight reported randomized trials have studied mammography’s effectiveness
in the United States,14,15 Sweden,16-20 Canada,21,22 and the United Kingdom.23 Concerns
related to flaws of these randomized clinical trials have been raised.24,25 In-depth independent reviews of the
criticisms of the trials have concluded that these flaws do not negate mammography’s
efficacy in reducing breast cancer mortality, especially in women aged 50
to 69 years.4,5,7,26 Trials
comparing mammography with or without clinical breast examination to usual
care (with little or no screening mammography) demonstrated remarkably consistent
results for women older than 50 years. Meta-analyses that included all trials
demonstrated statistically significant reductions of 20% to 35% in mortality
from breast cancer for women aged 50 to 69 years.7 The
majority of participants in clinical trials of mammography were white and
information on BRCA mutation status was not known.
In general, breast cancers detected by mammography screening are smaller
and have more favorable histological and biological features than tumors detected
between mammography screening rounds or tumors found outside of screening.27-32 Because
the favorable prognoses of women with breast cancer detected by mammography
screening may be attributable to selection bias, length bias, lead-time bias,
and overdiagnosis,33,34 randomized
controlled trials with breast cancer mortality as the outcome have been particularly
important in excluding such biases.
Quiz Ref IDThe benefit of screening women in their 40s is slower
to appear and is somewhat less than that of women older than 50 years. Women
in their 40s have a lower incidence of disease, denser breast tissue (which
can lower the sensitivity of mammography), and, on average, faster-growing
cancers.27,35,36 A
randomized trial of mammography screening for women in their early 40s is
under way in the United Kingdom.37 Clinicians
and patients are often surprised at the large number of women who need to
be screened to prevent 1 death due to breast cancer. For example, it has been
estimated that between 500 and 1800 women who are 40 years of age would need
to undergo regular screening mammography to prevent 1 breast cancer death
after 14 to 20 years.7,13
Randomized trials have included few or no women older than 70 years.
One case-control study found that screening women between 65 and 74 years
of age was associated with mortality reduction.38 Pooled
data from a community study showed that the sensitivity and specificity of
screening mammography were highest in older women, especially those older
than 80 years.36 Screening mammography may
not be beneficial for women with significant comorbidity or with a life expectancy
of less than 5 years, and may actually necessitate work-up that does not result
in any benefit.39-41 However,
if a woman is in reasonably good health and would be eligible for and interested
in treatment, continued screening should be supported. Encouraging individualized
decisions may be especially appropriate for women older than 70 years.42
The majority of women with abnormalities noted on screening mammograms
(≈ 95%) do not have breast cancer with variability based on multiple
factors including the radiologist’s assessment and the woman’s
age.7 Because the risk of breast cancer increases
with age, the likelihood of a woman with an abnormal mammogram result having
cancer also increases with age.43,44 On
the other hand, having a normal mammogram result does not rule out the possibility
of having breast cancer, because false-negative mammography examination results
do occur. In such cases, either the cancer is not visible on mammography examination
or the radiologist fails to notice the lesion prospectively.45-47
Results from 7 population-based community screening programs in the
United States on 463 372 screening mammograms revealed an overall sensitivity
of 75.0% and specificity of 92.3%.36 A sensitivity
of 75% means that 25% of women (or 25 of 100 women) who were diagnosed with
breast cancer had normal mammogram results between 12 and 24 months before
their cancer diagnosis (eg, false-negative examination result). This sensitivity
of 75% in the community was similar to that reported in the randomized trials
(68% to 88%) but the specificity was lower than in most of the trials (range,
82%-93% for Canadian National Breast Screening Study 1 to 98.5% for Health
Insurance Plan of New York).48
Breast density and age are important predictors of accuracy.36 Adjusted sensitivity ranged from 63% in women with
extremely dense breasts to 87% in women with almost entirely fatty breasts;
adjusted sensitivity increased with age from 69% in women aged 40 through
49 years to 83% in women aged 80 through 89 years.36 Adjusted
specificity increased from 89% in women with extremely dense breasts to 97%
in women with almost entirely fatty breasts.36
Guidelines for quality assurance have been issued by several bodies,
such as the Commission of the European Communities49,50 and
the US Mammography Quality Standards Act.51 The
Breast Imaging Reporting and Data System, used in the United States to standardize
reports, includes categories for assessment ranging from 0 to 552 (Table 1). The associated likelihood ratios for
a breast cancer diagnosis for first screen are shown in the table.54 Use of the Breast Imaging Reporting and Data System
has not eliminated the variability among radiologists55 that
had been noted before.56,57
Large differences have been noted between the recall rates (or percentage
of screening mammograms considered as positive) of community-based mammography
programs in the United States and those in other countries. The recall rate
in the United States is twice the recall rate in the United Kingdom (eg, 12.5%-14.4%
vs 7.6%), with no difference in cancer detection rate.58 Elmore
et al59 noted comparable differences between
North American screening programs and those in other locations, which persisted
after adjusting for differences such as age of women screened, use of single
vs double reading, and use of 1 vs 2 views of each breast for examinations.
Other possible reasons for the regional variability noted include differences
in the characteristics of the population screened (eg, presence of risk factors
or symptoms) and features of the mammography examination (eg, equipment type
and year, technician training).59,60 The
experience of the physician interpreting the mammograms has also been raised
as a possible reason for the variability.60-62 Recommendations
vary regarding the minimum number of mammograms that the physician should
interpret yearly, from 480 in the United States50 to
5000 in the United Kingdom.51 Educational training
has been shown to improve sensitivity with no change in specificity.63 Finally, features of the health care system, including
malpractice concerns, financial incentives, quality control procedures, and
auditing procedures, may be related to some of the variability.60
Double-reading of films, where 2 or more radiologists interpret each
film, is offered in some US screening programs and in about half of the other
countries that use mammography screening.4,58 However,
double reading is performed in various ways (eg, 2 interpretations may be
completely independent, 2 radiologists may perform interpretations together,
or a third reader may serve as a tie-breaker). A systematic review of 10 cohort
studies found that double reading increased the cancer detection rate by 3
to 11 per 10 000 women screened; recall rates increased or decreased
depending on the method of double reading used.64 The
heterogeneity of the definitions of double reading and of screening practices
precludes an accurate assessment of benefits and harms.
Full-Field Digital Mammography and Computer-Aided Detection Programs
Both screen-film mammography and full-field digital mammography use
x-rays to obtain images. With screen-film mammography the image is captured
on film; with full-field digital mammography the image is captured digitally.
Digital images can then be printed on film for viewing, or the images can
be interpreted directly from a computer monitor. The digital acquisition process
improves logistics and work flow by allowing electronic transmission, storage,
and retrieval. Radiologists viewing the image on a monitor can alter the contrast
and brightness of the image and magnify specific areas without additional
x-ray exposure. Digital imaging also allows easier use of computer-aided detection
software. One disadvantage, however, is the increased cost associated with
full-field digital mammography.4
Three community-based studies have compared full-field digital mammography
to screen-film mammography (Table 2).
Two studies found the sensitivity of full-field digital mammography (64% and
74%) to be less than that of screen-film mammography (79%, 90%), but these
studies had a small number of women with breast cancer (42 and 31, respectively)
and the display systems and experience of radiologists may have improved since
these studies.65,66,70 A
larger randomized study reported similar cancer detection rates (per all screened),
with higher recall rates for full-field digital mammography.67 A
trial now being conducted, which aimed to enroll 49 400 women, will compare
the diagnostic accuracy of full-field digital mammography from 4 different
manufacturers with that of traditional screen-film mammography.71
Computer-aided detection programs, which recognize patterns in breast
images associated with cancer (Figure 1),
may potentially help radiologists improve their diagnostic accuracy, but presently
data are limited (Table 2).68,69,72,73 Computer
programs that can mark calcifications, masses, or other potential lesions
on the mammogram may increase the number of cancers detected compared with
unassisted interpretations. In a study of 12 860 women,68 computer-aided
detection increased radiologists’ overall screening recall rate from
6.5% to 7.7% while increasing the number of cancers detected from 41 without
computer-aided detection to 49 with the technology. However, in the largest
clinical series to date, which included 59 139 mammograms interpreted
with computer-aided detection and 56 432 interpreted without, recall
rates and cancer detection rates did not differ significantly.69 Computer-aided
detection may prove helpful in reducing variability among radiologists of
differing expertise. Such programs are used by a small but growing number
of mammography facilities in the United States.69,74 Medicare
and Medicaid allow for additional billing for computer-aided interpretations
of mammograms. As technologies continue to improve, larger multisite studies
will be needed for more definitive evidence.
Clinical Breast Examination
Although two thirds of US women older than 40 years receive regular
screening clinical breast examinations,2 few
data about the efficacy of clinical breast examinations alone are available
from randomized clinical trials. Four randomized trials of mammography included
the clinical breast examination in the screened group.15,21-23 One
of these trials, the Canadian National Breast Screening Study 2 of women aged
50 through 59 years at entry, compared the results of an annual standardized
10- to 15-minute clinical breast examination and breast self-examination with
the results of an annual standardized clinical examination and breast self-examination
plus mammography (in other words, there was no typical control group that
received no screening).21 The trial found that
breast cancer mortality was similar in the 2 groups of women although yearly
mammography in addition to physical examination and breast self-examination
detected more small and lymph node–negative breast cancers than did
screening with physical examination alone.21 Although
the sensitivity of screening clinical breast examination was highest at 63%
in the National Breast Screening Study 2,75 an
overall estimate based on all randomized trials calculated sensitivity at
54% (95% confidence interval [CI], 48%-60%) and specificity at 94% (95% CI,
90%-97%).76
We suspect that few clinicians in the community setting perform examinations
as carefully as those in the Canadian trial, so accuracy may be lower in the
community setting. Results reported from community practices showed sensitivity
ranging from 28% to 36%77-79 (Table 3). In one study, two fifths of physicians
(34 out of 80) who performed a screening breast examination on manufactured
breast models used no discernible systematic search pattern at all.80 Sensitivity of examinations improved by spending
more time80,81 and by using a
thorough, systematic technique.76,82 However,
the number of false-positive examinations may increase with training.81
In randomized controlled trials, noting an abnormality on a screening
clinical breast examination in an asymptomatic average-risk woman increased
the likelihood of breast cancer (likelihood ratio [LR], 10.6; 95% CI, 5.8-19.2).76 However, in community practice, an abnormal screening
breast examination result was associated with an LR of 2.1,76 substantially
lower than that of women in the same practice presenting with a breast abnormality
(LR, 24).83 Noting a suspicious abnormality
on a screening mammogram was associated with LRs ranging from 7 to 2200 (Table 1).84
Breast self-examination is appealing as a patient-centered, noninvasive
procedure that allows women to become comfortable with their own bodies. However,
the extent of current practice is thought to be low.4 About
one third of US women regularly perform breast self-examination, and the estimated
sensitivity is low (20% to 30%).85 Among respondents
to the Women Physicians’ Health Study (N = 4501), only 21%
reported performing monthly breast self-examination.86
Training in breast self-examination, while associated with increased
accuracy of detection of lumps in breast tissue, has been associated with
increased rates of false-positive findings and thus diminished specificity.87-90 In
addition, there is evidence casting doubt on the benefits. A large randomized
controlled trial in Shanghai, China, of 266 064 women working in textile
factories provided half of the women with intensive initial instruction, including
practice with breast models, as well as regular reminders and practice examinations
under supervision once every 6 months for 5 years. This study found no positive
effect of breast self-examination on breast cancer mortality after 10 years
of follow-up but almost double the rate of biopsies due to false-positive
findings (1.8% of women in the instruction group vs 1.0% of women in the control
group).88,89 The study results
should be interpreted with caution because approximately 40% of women in the
trial were in their 30s. Also, it is possible that a 10-year follow-up was
not long enough to see an effect on breast cancer mortality.
A meta-analysis of the effect of regular breast self-examination on
breast cancer mortality or rates of advanced breast cancer (a marker of death)
was performed on 20 observational studies and 3 clinical trials.90 Bias
and confounding may affect the results of studies of women with breast cancer
who reported practicing self-examination before diagnosis. No difference in
death rate was noted in studies of women who detected their cancers during
self-examination (pooled relative risk [RR], 0.90; 95% CI, 0.72-1.12), and
no mortality differences were noted in trials of training (pooled RR, 1.01;
95% CI, 0.92-1.12).
Magnetic Resonance Imaging
Although screen-film mammography and full-field digital mammography
are the only imaging tools explicitly approved or grandfathered in for breast
cancer screening by the US Food and Drug Administration (FDA), other modalities
are under study.73 Those approved by the FDA
for diagnostic purposes (not screening) include MRI, ultrasound, scintimammography,
thermography, and electrical impedance imaging. Although mammography uses
x-ray and sonography uses sound waves to create images, MRI produces images
from the combination of a strong magnetic field, radio waves, and computer
processing (Figure 2).
Screening MRI may be helpful for women for whom mammography is not optimal,
such as young women at substantially increased risk for breast cancer because
of known BRCA1 or BRCA2 mutations.
Available data are limited to studies of test characteristics in women at
high risk (Table 4),91-98 and
the impact on breast cancer mortality has not been determined. Both retrospective
and prospective cohorts have been described. The small number of cases with
breast cancer in these studies (the range among studies was 3 to 45 women)
means that estimates of sensitivity were not precise. Nevertheless, every
study reported higher sensitivity for breast MRI than for mammography, ultrasound,
or both.91-98 The
largest study reported on 1909 women at increased risk in the Netherlands,
with 45 women diagnosed with cancer who had all screening examinations.96 The sensitivity of clinical breast examination, mammography,
and MRI in this study was 17.9%, 40%, and 71%, respectively. The overall discriminating
capacity of MRI was significantly better compared with mammography as assessed
by receiver operating characteristic curves (area under the curve 0.827 for
MRI vs 0.686 for mammography).
Specificity of MRI tends to be lower than that of mammography; however,
data are not consistently presented and specificity is not always easy to
calculate. In the study of 1909 women in the Netherlands, the specificity
of clinical breast examination, mammography, and MRI was 98.1%, 95.0%, and
89.8%, respectively,96 and the authors noted
that screening with MRI led to twice as many unneeded additional examinations
(420 vs 207) and 3 times as many unneeded biopsies (24 vs 7) as did screening
with mammography.96 Warner et al98 reported
a substantial recall rate in the first round of MRI screening (26%), which
decreased to 10% in the third round of MRI screening. Additional studies of
MRI screening among high-risk women are under way.99
Quiz Ref IDMagnetic resonance imaging has not been studied in
the general population as a screening tool, and the results from MRI screening
of high-risk women may not apply to women at average risk. The high cost of
MRI (approximately 10 times the cost of mammography) and its relatively low
specificity (compared with mammography) probably prohibit its routine use
for screening general populations. Also, MRI is time-consuming, requires intravenous
contrast administration, and may be problematic for claustrophobic patients.
Ultrasound, frequently used as a targeted diagnostic examination focusing
on a specific area of concern,100 may help
distinguish between cyst and solid masses and also between benign and malignant
masses.101 Breast ultrasound data are available
from diagnostic populations, with screening studies limited to women with
dense breasts on mammography or at increased risk for breast cancer.102 Although ultrasound may detect 3 to 4 additional
breast cancers per 1000 women in these increased-risk populations,93,100,101,103-108 there
are no data on the use of screening ultrasound in the general population.
Breast ultrasound has limitations as a potential screening tool because it
requires a well-trained skilled operator. Examination techniques are not standardized,
interpretation criteria are variable, and breast ultrasound does not consistently
detect microcalcifications. Preliminary data suggest a higher rate of false-positive
examination results with ultrasound than with mammography alone.100,104-106 For
example, the false-positive rate (based on solid lesion for ultrasound) ranged
from 2.4% to 12.9% for ultrasound and 0.7% to 6% for mammography.102
National Screening Guidelines
All groups recommend screening mammography for women aged 50 through
69 years.7 Within the United States, all recommend
it for women in their 40s, but vary in the screening intervals recommended
and encourage “informed decision making” with all women about
the choice. Being older than 70 years should not preclude women from continuing
to undergo screening; however, decisions regarding continued screening should
include life expectancy and health status.7,41 International
policies differ with respect to the target age group to be screened, the intervals
between screening, the number of mammographic views taken per breast, and
the screening modalities recommended.4 Clinical
breast examination is recommended by some,109 but
not all, groups. Most national groups no longer recommend breast self-examination,
but some encourage women to become familiar with the contour of their own
breasts.42,109 Other imaging modalities,
such as MRI and ultrasound, are not recommended for screening the general
population. (See http://www.Guidelines.gov.)
The primary goal of breast cancer screening is to reduce subsequent
breast cancer mortality through early detection. Theoretically this should
translate into reduced morbidity from the disease.110 In
addition, many women report feeling reassured by screening,111 especially
after having a so-called normal screen result.112
Possible harms include pain and discomfort, especially noted during
compression of breast tissue during mammography. Compression of breast tissue
reduces motion artifact and improves image quality. Reports of the level of
discomfort, however, vary widely.113-115 Anxiety
about screening is another concern.116,117Quiz Ref IDBreast cancer screening yields both false-positive and false-negative
results. False-positive results have been associated with anxiety, additional
costs, and morbidity.117,118 After
10 years of annual screening in the United States, it is estimated that 1
in 2 women will have at least 1 false-positive mammogram result, and 1 in
5 women will have at least 1 false-positive clinical breast examination result.118 False-negative mammography examinations occur in
approximately 20% to 40% of women with breast cancer.36
Overdiagnosis and overtreatment of clinically insignificant disease
is possible, especially ductal carcinoma in situ noted by mammography.119,120 Theoretical concerns about radiation-induced
breast cancer from exposure to repeated mammography have been raised, but
the potential benefits are thought to outweigh the risks. For example, the
benefit-to-harm ratio is estimated to be 48.5 lives saved per 1 life lost
due to radiation exposure.121 A mortality paradox
has been noted in women aged 40 through 49 years, whereby increased mortality
is noted among women screened for the first 3 to 10 years after the initiation
of screening.122-124 Tumor
dissemination after needle biopsy has also been suggested although the clinical
significance is unclear.125
Observer variability among radiologists who interpret mammography examinations
has been noted both in a test situation and in community practices.55-57,126 A
decision to perform a breast biopsy may depend heavily on the radiologist’s
interpretation; therefore, interpretive variability can directly affect patient
management.126
The benefit-to-harm ratio of screening increases as women age because
screening accuracy improves and prevalence of breast cancer increases. Younger
women, however, have more potential years of life to be gained from screening.
Communicating With Patients
Effective communication of information on benefits and harms is challenging.
Multiple studies document inaccurate or incomplete comprehension of risk information,
cognitive biases that affect how patients process risk information, and poor
communication skills on the part of physicians.127-130 Use
of frequencies with specific reference groups (“23 out of 1000 women
your age”) instead of percentages (“0.23%”) may facilitate
the comparison of small risks.131-133 Presentation
of both positive (“23 in 1000 women your age will develop breast cancer”)
and negative framing (“977 in 1000 women your age will not develop breast
cancer”) can reduce biases in decision making.130,132 Visual
aids, such as bar graphs or pie charts, can increase the comprehension and
saliency of information.134 Risk-prediction
models can be used to calculate the probability of being diagnosed with breast
cancer (Box). Effective physician-patient
partnership, for which gaps in comprehension are frequently assessed and resolved
may have the greatest impact on patients’ understanding of information.135
Reviews of breast cancer screening usually concentrate on the results
of randomized trials of mammography to reduce breast cancer mortality. We
have emphasized data on effectiveness in the community setting among the general
population of women, which can often be different from the ideal setting of
a randomized trial or the setting of a study among high-risk women. We have
also emphasized the challenge of evaluating new screening modalities. Newer
screening tests such as MRI and ultrasound have been studied in women at increased
risk of breast cancer (eg, carriers of BRCA1 or BRCA2 mutations). None of the newer tests has been evaluated
for its effect on breast cancer mortality in the general population and no
data support screening the general population with these technologies. Careful
evaluation of newer modalities in the populations for which they will be used
is critical, especially since these modalities are usually more expensive
than current approaches and the risk of increased false-positives is present.
An overview of breast cancer screening modalities is shown in Table 5.
Most national groups recommend screening with mammography, with or without
clinical breast examination, beginning at 40 years of age. Data on clinical
breast examination as performed in the community suggest a lower level of
cancer detection than would be anticipated from trials. Breast self-examination
is no longer recommended by most expert groups. Limitations and potential
harms have been identified for all existing screening tools. Quality control
needs to be emphasized for established screening methods.
Corresponding Author: Joann G. Elmore, MD,
MPH, Harborview Medical Center, 325 Ninth Ave, Box 359780, Seattle, WA 98104
(jelmore@u.washington.edu).
Author Contributions: Dr Elmore had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Elmore, Lehman, Armstrong,
Fletcher.
Analysis and interpretation of data: Elmore,
Lehman, Armstrong, Fletcher.
Drafting of the manuscript: Elmore, Lehman.
Critical revision of the manuscript for important
intellectual content: Elmore, Lehman, Armstrong, Fletcher.
Administrative, technical, or material support:
Elmore, Lehman.
Study supervision: Elmore, Lehman, Armstrong.
Financial Disclosure: Dr Armstrong has served
as an expert witness about breast cancer risk. No other authors reported any
disclosures.
Funding/Support: Dr Elmore was supported by
grant K05-CA10469 from the National Cancer Institute. Dr Armstrong was supported
by the Robert Wood Johnson Generalist Physician Award.
Role of the Sponsor: The Robert Wood Johnson
Foundation did not participate in the design and conduct of the study; in
the collection, analysis, and interpretation of the data; or in the preparation,
review, or approval of the manuscript.
Disclaimer: The views expressed in this article
are those of the authors and do not necessarily reflect the opinion of the
Robert Wood Johnson Foundation.
Acknowledgment: We thank Carol Munch and Sue
Peacock for their administrative assistance.
1.Adair FE. Clinical manifestations of early cancer of the breast.
N Engl J Med. 1933;208:1250-1255
Google ScholarCrossref 2.Blackman DK, Bennett EM, Miller DS. Trends in self-reported use of mammograms (1989-1997) and papanicolaou
tests (1991-1997): Behavioral Risk Factor Surveillance System.
MMWR CDC Surveill Summ. 1999;48:1-2210526871
Google Scholar 3.Weir HK, Thun MJ, Hankey BF.
et al. Annual report to the nation on the status of cancer, 1975-2000, featuring
the uses of surveillance data for cancer prevention and control.
J Natl Cancer Inst. 2003;95:1276-129912953083
Google ScholarCrossref 4.Vainio H, Bianchini F. Breast Cancer Screening: International Agency for
Research on Cancer (IARC) Handbooks of Cancer Prevention. Vol 7. Lyon, France: IARC Press; 2002
5.US Preventive Services Task Force. Screening for breast cancer: recommendations and rationale.
Ann Intern Med. 2002;137:344-34612204019
Google ScholarCrossref 6.US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Alexandria, Va: International Medical Publishing Inc; 1996
7.Fletcher SW, Elmore JG. Clinical practice: mammographic screening for breast cancer.
N Engl J Med. 2003;348:1672-168012711743
Google ScholarCrossref 8.Last JM. A Dictionary of Epidemiology. New York, NY: Oxford University Press; 1995:52
9.Peto R, Boreham J, Clarke M, Davies C, Beral V. UK and USA breast cancer deaths down 25% in year 2000 at ages 20-69
years.
Lancet. 2000;355:182210832853
Google ScholarCrossref 10.Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials.
Lancet. 1998;351:1451-14679605801
Google ScholarCrossref 11.Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised
trials.
Lancet. 1998;352:930-9429752815
Google ScholarCrossref 12.Barlow WE, Lehman CD, Zheng Y.
et al. Performance of diagnostic mammography in women with signs or symptoms
of breast cancer.
J Natl Cancer Inst. 2002;94:1151-115912165640
Google ScholarCrossref 13.Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the U.S Preventive
Services Task Force.
Ann Intern Med. 2002;137:347-36012204020
Google ScholarCrossref 14.Shapiro S, Venet W, Strax P, Venet L. Current results of the breast cancer screening randomized trial: the
health insurance plan (HIP) of greater New York study. In: Day NE, Miller AB, eds. Screening for Breast
Cancer. Toronto, Ontario: Hans Harbor; 1988:3-15
15.Shapiro S, Venet W, Strax P, Venet L. Periodic Screening for Breast Cancer: The Health
Insurance Plan Project and Its Sequelae, 1963-1986. Baltimore, Md: Johns Hopkins University Press; 1988
16.Nystrom L, Andersson I, Bjurstam N, Frisell J, Nordenskjold B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the
Swedish randomised trials.
Lancet. 2002;359:909-91911918907
Google ScholarCrossref 17.Andersson I, Janzon L. Reduced breast cancer mortality in women under age 50: updated results
from the Malmo Mammographic Screening Program.
J Natl Cancer Inst Monogr. 1997;63-679709278
Google Scholar 18.Tabar L, Fagerberg G, Chen HH.
et al. Efficacy of breast cancer screening by age: new results from the Swedish
Two-County Trial.
Cancer. 1995;75:2507-25177736395
Google ScholarCrossref 19.Frisell J, Lidbrink E. The Stockholm Mammographic Screening Trial: risks and benefits in age
group 40-49 years.
J Natl Cancer Inst Monogr. 1997;49-519709275
Google Scholar 20.Bjurstam N, Bjorneld L, Duffy SW.
et al. The Gothenburg Breast Cancer Screening Trial: preliminary results on
breast cancer mortality for women aged 39-49.
J Natl Cancer Inst Monogr. 1997;53-559709276
Google Scholar 21.Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2: 13-year results of a randomized
trial in women aged 50-59 years.
J Natl Cancer Inst. 2000;92:1490-149910995804
Google ScholarCrossref 22.Miller AB, To T, Baines CJ, Wall C. 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. 2002;137:305-31512204013
Google ScholarCrossref 23.Alexander FE, Anderson TJ, Brown HK.
et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer
screening.
Lancet. 1999;353:1903-190810371567
Google ScholarCrossref 24.Olsen O, Gøtzsche PC. Cochrane review on screening for breast cancer with mammography.
Lancet. 2001;358:1340-134211684218
Google ScholarCrossref 25.Olsen O, Gøtzsche PC. Screening for breast cancer with mammography. Oxford, England: Cochrane Library, Update Software; Issue 3: 2003
26. The Benefit of Population Screening for Breast Cancer
with Mammography. The Hague, the Netherlands: Health Council of the Netherlands; 2002.
Publication 2002/3E
27.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. 1999;91:2020-202810580027
Google ScholarCrossref 28.Crosier M, Scott D, Wilson RG, Griffiths CD, May FE, Westley BR. Differences in Ki67 and c-erbB2 expression between screen-detected
and true interval breast cancers.
Clin Cancer Res. 1999;5:2682-268810537329
Google Scholar 29.Klemi PJ, Joensuu H, Toikkanen S.
et al. Aggressiveness of breast cancers found with and without screening.
BMJ. 1992;304:467-4691547414
Google ScholarCrossref 30.Gilliland FD, Joste N, Stauber PM.
et al. Biologic characteristics of interval and screen-detected breast cancers.
J Natl Cancer Inst. 2000;92:743-74910793111
Google ScholarCrossref 31.Groenendijk RP, Bult P, Tewarie L.
et al. Screen-detected breast cancers have a lower mitotic activity index.
Br J Cancer. 2000;82:381-38410646892
Google ScholarCrossref 32.Joensuu H, Lehtimäki T, Holli K.
et al. Risk for distant recurrence of breast cancer detected by mammography
screening or other methods.
JAMA. 2004;292:1064-107315339900
Google ScholarCrossref 33.Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction
of nationwide screening: prospective cohort study.
BMJ. 2004;328:921-92415013948
Google ScholarCrossref 34.Welch HG. Should I Be Tested for Cancer? Maybe Not and Here's
Why. Berkeley: University of California Press; 2004
35.Ries LAG, Eisner MP, Kosary CL.
et al. SEER Cancer Statistics Review, 1975-2001. Bethesda, Md: National Cancer Institute; 2004
36.Carney PA, Miglioretti DL, Yankaskas BC.
et al. Individual and combined effects of age, breast density, and hormone
replacement therapy use on the accuracy of screening mammography.
Ann Intern Med. 2003;138:168-17512558355
Google ScholarCrossref 37.Moss S.Trial Steering Group. A trial to study the effect on breast cancer mortality of annual mammographic
screening in women starting at age 40.
J Med Screen. 1999;6:144-14810572845
Google ScholarCrossref 38.Van Dijck JA, Verbeek AL, Beex LV.
et al. Mammographic screening after the age of 65 years: evidence for a reduction
in breast cancer mortality.
Int J Cancer. 1996;66:727-7318647640
Google ScholarCrossref 39.Satariano WA, Ragland DR. The effect of comorbidity on 3-year survival of women with primary
breast cancer.
Ann Intern Med. 1994;120:104-1108256968
Google ScholarCrossref 40.Walter LC, Eng C, Covinsky KE. Screening mammography for frail older women: what are the burdens?
J Gen Intern Med. 2001;16:779-78411722693
Google ScholarCrossref 41.Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized
decision making.
JAMA. 2001;285:2750-275611386931
Google ScholarCrossref 42.Smith R, Saslow D, Sawyer KA.
et al. American Cancer Society guidelines for breast cancer screening: update
2003.
CA Cancer J Clin. 2003;53:141-16912809408
Google ScholarCrossref 43.Kerlikowske K, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family
history of breast cancer.
JAMA. 1993;270:2444-24508230621
Google ScholarCrossref 44.Brown ML, Houn F, Sickles EA, Kessler LG. Screening mammography in community practice: positive predictive value
of abnormal findings and yield of follow-up diagnostic procedures.
AJR Am J Roentgenol. 1995;165:1373-13777484568
Google ScholarCrossref 45.Ma L, Fishell E, Wright B, Hanna W, Allan S, Boyd NF. Case-control study of factors associated with failure to detect breast
cancer by mammography.
J Natl Cancer Inst. 1992;84:781-7851573665
Google ScholarCrossref 46.Harvey JA, Fajardo LL, Innis CA. Previous mammograms in patients with impalpable breast carcinoma: retrospective
vs blinded interpretation.
AJR Am J Roentgenol. 1993;161:1167-11728249720
Google ScholarCrossref 47.Ikeda DM, Andersson I, Wattsgård C, Janzon L, Linell F. Interval carcinomas in the Malmö Mammographic Screening Trial:
radiographic appearance and prognostic considerations.
AJR Am J Roentgenol. 1992;159:287-2941632342
Google ScholarCrossref 48.Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Report of the International Workshop on Screening for Breast Cancer.
J Natl Cancer Inst. 1993;85:1644-16568105098
Google ScholarCrossref 49.Commission of the European Communities. European Guidelines for Quality Assurance in Mammography
Screening. 3rd ed. Luxembourg: Office for Official Publications of the European
Communities; 2001
51. Quality mammography standards—FDA; final rule.
Federal Register. 1997;62:55852-5599410177306
Google Scholar 52.American College of Radiology. Illustrated Breast Imaging Reporting and Data System
(BI-RADS). 3rd ed. Reston, Va: American College of Radiology; 1998
53.D'Orsi CJ, Bassett LW, Feig SA.
et al. Breast Imaging Reporting and Data System. 3rd ed. Reston, Va: American College of Radiology; 1998
54.Kerlikowske K, Smith-Bindman R, Ljung BM, Grady D. Evaluation of abnormal mammography results and palpable breast abnormalities.
Ann Intern Med. 2003;139:274-28412965983
Google ScholarCrossref 55.Kerlikowske K, Grady D, Barclay J.
et al. Variability and accuracy in mammographic interpretation using the American
College of Radiology Breast Imaging Reporting and Data System.
J Natl Cancer Inst. 1998;90:1801-18099839520
Google ScholarCrossref 56.Elmore JG, Wells CK, Lee CH, Howard DH, Feinstein AR. Variability in radiologists' interpretations of mammograms.
N Engl J Med. 1994;331:1493-14997969300
Google ScholarCrossref 57.Beam CA, Layde PM, Sullivan DC. Variability in the interpretation of screening mammograms by US radiologists:
findings from a national sample.
Arch Intern Med. 1996;156:209-2138546556
Google ScholarCrossref 58.Smith-Bindman R, Chu PW, Miglioretti DL.
et al. Comparison of screening mammography in the United States and the United
Kingdom.
JAMA. 2003;290:2129-213714570948
Google ScholarCrossref 59.Elmore JG, Nakano CY, Koepsell TD, Desnick LM, D'Orsi CJ, Ransohoff DF. International variation in screening mammography interpretations in
community-based programs.
J Natl Cancer Inst. 2003;95:1384-139313130114
Google ScholarCrossref 60.Elmore JG, Miglioretti DL, Carney PA. Does practice make perfect when interpreting mammography? II.
J Natl Cancer Inst. 2003;95:250-25212591973
Google ScholarCrossref 61.Esserman L, Cowley H, Eberle C.
et al. Improving the accuracy of mammography: volume and outcome relationships.
J Natl Cancer Inst. 2002;94:369-37511880475
Google ScholarCrossref 62.Beam CA, Conant EF, Sickles EA. Association of volume and volume-independent factors with accuracy
in screening mammogram interpretation.
J Natl Cancer Inst. 2003;95:282-29012591984
Google ScholarCrossref 63.Linver MN, Paster SB, Rosenberg RD, Key CR, Stidley CA, King WV. Improvement in mammography interpretation skills in a community radiology
practice after dedicated teaching courses: 2-year medical audit of 38,633
cases.
Radiology. 1992;184:39-431609100
Google Scholar 64.Dinnes J, Moss S, Melia J, Blanks R, Song F, Kleijnen J. Effectiveness and cost-effectiveness of double reading of mammograms
in breast cancer screening: findings of a systematic review.
Breast. 2001;10:455-46314965624
Google ScholarCrossref 65.Lewin JM, D'Orsi CJ, Hendrick RE.
et al. Clinical comparison of full-field digital mammography and screen-film
mammography for detection of breast cancer.
AJR Am J Roentgenol. 2002;179:671-67712185042
Google ScholarCrossref 66.Skaane P, Young K, Skjennald A. Population-based mammography screening: comparison of screen-film and
full-field digital mammography with soft-copy reading—Oslo I Study.
Radiology. 2003;229:877-88414576447
Google ScholarCrossref 67.Skaane P, Skjennald A. Screen-film mammography versus full-field digital mammography with
soft-copy reading: randomized trial in a population-based screening program—the
Oslo II Study.
Radiology. 2004;232:197-20415155893
Google ScholarCrossref 68.Freer TW, Ulissey MJ. Screening mammography with computer-aided detection: prospective study
of 12,860 patients in a community breast center.
Radiology. 2001;220:781-78611526282
Google ScholarCrossref 69.Gur D, Sumkin JH, Rockette HE.
et al. Changes in breast cancer detection and mammography recall rates after
the introduction of a computer-aided detection system.
J Natl Cancer Inst. 2004;96:185-19014759985
Google ScholarCrossref 70.Lewin JM, Hendrick RE, D'Orsi CJ.
et al. Comparison of full-field digital mammography with screen-film mammography
for cancer detection: results of 4,945 paired examinations.
Radiology. 2001;218:873-88011230669
Google Scholar 71. Digital versus film-screen mammography [ACRIN protocol 6652].
Philadelphia, Pa: American College of Radiology Imaging Network (ACRIN).
October 27, 2003. Available at: http://www.acrin.org/current_protocols.html. Accessibility verified February 2, 2005 72.Huo Z, Giger ML, Vyborny CJ, Metz CE. Breast cancer: effectiveness of computer-aided diagnosis observer study
with independent database of mammograms.
Radiology. 2002;224:560-56812147857
Google ScholarCrossref 73.Nass S, Henderson C. Mammography and Beyond: Developing Technologies for
the Early Detection of Breast Cancer. Washington, DC: National Academy Press; 2001
74.Hendrick RE, Cutter GR, Berns EA.
et al. Community-based mammography practice: services, charges, and interpretation
methods.
AJR Am J Roentgenol. 2005;184:433-43815671359
Google ScholarCrossref 75.Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Report of the International Workshop on Screening for Breast Cancer.
J Natl Cancer Inst. 1993;85:1644-16568105098
Google ScholarCrossref 76.Barton MB, Harris R, Fletcher SW. Does this patient have breast cancer? the screening clinical breast
examination: should it be done? how?
JAMA. 1999;282:1270-128010517431
Google ScholarCrossref 77.Bobo JK, Lee NC, Thames SF. Findings from 752,081 clinical breast examinations reported to a national
screening program from 1995 through 1998.
J Natl Cancer Inst. 2000;92:971-97610861308
Google ScholarCrossref 78.Oestreicher N, White E, Lehman CD, Mandelson MT, Porter PL, Taplin SH. Predictors of sensitivity of clinical breast examination (CBE).
Breast Cancer Res Treat. 2002;76:73-8112408378
Google ScholarCrossref 79.Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination,
and breast US and evaluation of factors that influence them: an analysis of
27,825 patient evaluations.
Radiology. 2002;225:165-17512355001
Google ScholarCrossref 80.Fletcher SW, O'Malley MS, Bunce LA. Physicians' abilities to detect lumps in silicone breast models.
JAMA. 1985;253:2224-22283974114
Google ScholarCrossref 81.Campbell HS, Fletcher SW, Pilgrim CA, Morgan TM, Lin S. Improving physicians' and nurses' clinical breast examination:
a randomized controlled trial.
Am J Prev Med. 1991;7:1-81867894
Google Scholar 82.Saunders KJ, Pilgrim CA, Pennypacker HS. Increased proficiency of search in breast self-examination.
Cancer. 1986;58:2531-25373768844
Google ScholarCrossref 83.Barton MB, Elmore JG, Fletcher SW. Breast symptoms among women enrolled in a health maintenance organization:
frequency, evaluation, and outcome.
Ann Intern Med. 1999;130:651-65710215561
Google ScholarCrossref 84.Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Likelihood ratios for modern screening mammography: risk of breast
cancer based on age and mammographic interpretation.
JAMA. 1996;276:39-438667537
Google ScholarCrossref 85.O'Malley MS, Fletcher SW.US Preventive Services Task Force. Screening for breast cancer with breast self-examination: a critical
review.
JAMA. 1987;257:2196-22033550165
Google ScholarCrossref 86.Frank E, Rimer BK, Brogan D, Elon L. US women physicians' personal and clinical breast cancer screening
practices.
J Womens Health Gend Based Med. 2000;9:791-80111025871
Google ScholarCrossref 87.Hall DC, Adams CK, Stein GH, Stephenson HS, Goldstein MK, Pennypacker HS. Improved detection of human breast lesions following experimental training.
Cancer. 1980;46:408-4147388779
Google ScholarCrossref 88.Thomas DB, Gao DL, Self SG.
et al. Randomized trial of breast self-examination in Shanghai: methodology
and preliminary results.
J Natl Cancer Inst. 1997;89:355-3659060957
Google ScholarCrossref 89.Thomas DB, Gao DL, Ray RM.
et al. Randomized trial of breast self-examination in Shanghai: final results.
J Natl Cancer Inst. 2002;94:1445-145712359854
Google ScholarCrossref 90.Hackshaw AK, Paul EA. Breast self-examination and death from breast cancer: a meta-analysis.
Br J Cancer. 2003;88:1047-105312671703
Google ScholarCrossref 91.Kuhl CK, Schmutzler RK, Leutner CC.
et al. Breast MR imaging screening in 192 women proved or suspected to be
carriers of a breast cancer susceptibility gene: preliminary results.
Radiology. 2000;215:267-27910751498
Google Scholar 92.Tilanus-Linthorst MM, Obdeijn IM, Bartels KC, de Koning HJ, Oudkerk M. First experiences in screening women at high risk for breast cancer
with MR imaging.
Breast Cancer Res Treat. 2000;63:53-6011079159
Google ScholarCrossref 93.Warner E, Plewes DB, Shumak RS.
et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound
for surveillance of women at high risk for hereditary breast cancer.
J Clin Oncol. 2001;19:3524-353111481359
Google Scholar 94.Morris EA, Liberman L, Ballon DJ.
et al. MRI of occult breast carcinoma in a high-risk population.
AJR Am J Roentgenol. 2003;181:619-62612933450
Google ScholarCrossref 95.Podo F, Sardanelli F, Canese R.
et al. The Italian multi-centre project on evaluation of MRI and other imaging
modalities in early detection of breast cancer in subjects at high genetic
risk.
J Exp Clin Cancer Res. 2002;21:(3 suppl)
115-12412585665
Google Scholar 96.Kriege M, Brekelmans CT, Boetes C.
et al. Efficacy of MRI and mammography for breast-cancer screening in women
with a familial or genetic predisposition.
N Engl J Med. 2004;351:427-43715282350
Google ScholarCrossref 97.Stoutjesdijk MJ, Boetes C, Jager GJ.
et al. Magnetic resonance imaging and mammography in women with a hereditary
risk of breast cancer.
J Natl Cancer Inst. 2001;93:1095-110211459871
Google ScholarCrossref 98.Warner E, Plewes DB, Hill KA.
et al. Surveillance of
BRCA1 and
BRCA2 mutation carriers with magnetic resonance imaging, ultrasound,
mammography, and clinical breast examination.
JAMA. 2004;292:1317-132515367553
Google ScholarCrossref 99.Leach MO, Eeles RA, Turnbull LW.
et al. The UK national study of magnetic resonance imaging as a method of
screening for breast cancer (MARIBS).
J Exp Clin Cancer Res. 2002;21:(3 suppl)
107-11412585664
Google Scholar 100.Gordon PB. Ultrasound for breast cancer screening and staging.
Radiol Clin N Am. 2002;40:431-44112117185
Google ScholarCrossref 101.Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonography to distinguish between benign
and malignant lesions.
Radiology. 1995;196:123-1347784555
Google Scholar 102.Irwig L, Houssami N, van Vliet C. New technologies in screening for breast cancer: a systematic review
of their accuracy.
Br J Cancer. 2004;90:2118-212215150556
Google Scholar 103.Gordon PB, Goldenberg SL. Malignant breast masses detected only by ultrasound: a retrospective
review.
Cancer. 1995;76:626-6308625156
Google ScholarCrossref 104.Kolb TM, Lichy J, Newhouse JH. Occult cancer in women with dense breasts: detection with screening
US—diagnostic yield and tumor characteristics.
Radiology. 1998;207:191-1999530316
Google Scholar 105.Buchberger W, DeKoekkoek-Doll P, Springer P, Obrist P, Dunser M. Incidental findings on sonography of the breast: clinical significance
and diagnostic workup.
AJR Am J Roentgenol. 1999;173:921-92710511149
Google ScholarCrossref 106.Kaplan SS. The utility of bilateral whole breast ultrasound in the evaluation
of women with dense breast tissue [abstract].
Radiology. 2000;217:318
Google Scholar 107.Hou MF, Chuang HY, Ou-Yang F.
et al. Comparison of breast mammography, sonography and physical examination
for screening women at high risk of breast cancer in Taiwan.
Ultrasound Med Biol. 2002;28:415-42012049952
Google ScholarCrossref 108.O'Driscoll D, Warren R, MacKay J, Britton P, Day NE. Screening with breast ultrasound in a population at moderate risk due
to family history.
J Med Screen. 2001;8:106-10911480440
Google ScholarCrossref 109.National Guidelines Clearinghouse Web site. Breast cancer screening.
Available at: http://www.guidelines.gov. Accessibility
verified February 2, 2005 110.Freedman GM, Anderson PR, Goldstein LJ.
et al. Routine mammography is associated with earlier stage disease and greater
eligibility for breast conservation in breast carcinoma patients age 40 years
and older.
Cancer. 2003;98:918-92512942557
Google ScholarCrossref 111.Baines C, To T, Wall C. Women's attitudes to screening after participation in the National
Breast Screening Study: a questionnaire survey.
Cancer. 1990;65:1663-16692311075
Google ScholarCrossref 112.Bartolucci G, Savron G, Fava GA, Grandi S, Trombini G, Orlandi C. Psychological reactions to thermography and mammography.
Stress Med. 1989;5:195-199
Google ScholarCrossref 113.Rutter DR, Calnan M, Vaile MS, Field S, Wade KA. Discomfort and pain during mammography: description, prediction, and
prevention.
BMJ. 1992;305:443-4451392955
Google ScholarCrossref 114.Kornguth PJ, Keefe FJ, Conaway MR. Pain during mammography: characteristics and relationship to demographic
and medical variables.
Pain. 1996;66:187-1948880840
Google ScholarCrossref 115.Dullum JR, Lewis EC, Mayer JA. Rates and correlates of discomfort associated with mammography.
Radiology. 2000;214:547-55210671609
Google Scholar 116.Gram IT, Slenker SE. Cancer anxiety and attitudes toward mammography among screening attenders,
nonattenders, and women never invited.
Am J Public Health. 1992;82:249-2511739156
Google ScholarCrossref 117.Lerman C, Trock B, Rimer BK, Boyce A, Jepson C, Engstrom PF. Psychological and behavioral implications of abnormal mammograms.
Ann Intern Med. 1991;114:657-6612003712
Google ScholarCrossref 118.Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false-positive screening mammograms and clinical breast
examinations.
N Engl J Med. 1998;338:1089-10969545356
Google ScholarCrossref 119.Ernster VL, Barclay J. Increases in ductal carcinoma in situ (DCIS) of the breast in relation
to mammography: a dilemma.
J Natl Cancer Inst Monogr. 1997;151-1569709292
Google Scholar 120.Ernster VL, Barclay J, Kerlikowske J, Grady D, Henderson IC. Incidence of and treatment for ductal carcinoma in situ of the breast.
JAMA. 1996;275:913-9188598618
Google ScholarCrossref 121.Feig SA, Hendrick RE. Radiation risk from screening mammography of women aged 40-49 years.
J Natl Cancer Inst Monogr. 1997;119-1249709287
Google Scholar 122.Baines CJ. Mammography screening: are women really giving informed consent?
J Natl Cancer Inst. 2003;95:1508-151114559870
Google ScholarCrossref 123.Baines CJ. Mammography screening: are women really giving informed consent? (countering
the counterpoint).
J Natl Cancer Inst. 2003;95:1512-151314559872
Google ScholarCrossref 124.Berg AO. Mammography screening: are women really giving informed consent? (counterpoint).
J Natl Cancer Inst. 2003;95:1511-151214559871
Google ScholarCrossref 125.Hansen NM, Ye X, Grube BJ, Giuliano AE. Manipulation of the primary breast tumor and the incidence of sentinel
node metastases from invasive breast cancer.
Arch Surg. 2004;139:634-63915197090
Google ScholarCrossref 126.Boyd NF, Wolfson C, Moskowitz M.
et al. Observer variation in the interpretation of xeromammograms.
J Natl Cancer Inst. 1982;68:357-3637038244
Google Scholar 127.Thornton H. Patients' understanding of risk: enabling understanding must not
lead to manipulation.
BMJ. 2003;327:693-69414512450
Google ScholarCrossref 128.Schwartz LM, Woloshin S, Black WC, Welch HG. The role of numeracy in understanding the benefit of screening mammography.
Ann Intern Med. 1997;127:966-9729412301
Google ScholarCrossref 129.Braddock CH III, Edwards KA, Hasenberg NM, Laidley TL, Levinson W. Informed decision making in outpatient practice: time to get back to
basics.
JAMA. 1999;282:2313-232010612318
Google ScholarCrossref 130.Edwards A, Elwyn G, Covey J, Matthews E, Pill R. Presenting risk information—a review of the effects of “framing”
and other manipulations on patient outcomes.
J Health Commun. 2001;6:61-8211317424
Google ScholarCrossref 132.Gigerenzer G, Edwards A. Simple tools for understanding risks: from innumeracy to insight.
BMJ. 2003;327:741-74414512488
Google ScholarCrossref 133.Hoffrage U, Lindsey S, Hertwig R, Gigerenzer G. Communicating statistical information.
Science. 2000;290:2261-226211188724
Google ScholarCrossref 134.Edwards A, Elwyn G, Mulley A. Explaining risks: turning numerical data into meaningful pictures.
BMJ. 2002;324:827-83011934777
Google ScholarCrossref 135.Alaszewski A, Horlick-Jones T. How can doctors communicate information about risk more effectively?
BMJ. 2003;327:728-73114512483
Google ScholarCrossref