MRI indicates magnetic resonance imaging.
The area under the receiver operating characteristic curve is 0.88 (95%
confidence interval [CI], 0.86-0.91) for overall; 0.88 (95% CI, 0.84-0.93)
for microcalcifications present; and 0.88 (95% CI, 0.85-0.91) for microcalcifications
absent. MRI indicates magnetic resonance imaging.
The area under the receiver operating characteristic curve is 0.90 (95%
confidence interval [CI], 0.83-0.96) for mostly fat; 0.91 (95% CI, 0.87-0.95)
for scattered fibroglandular tissue; 0.87 (95% CI, 0.83-0.91) for heterogeneously
dense; and 0.84 (95% CI, 0.74-0.93) for extremely dense. MRI indicates magnetic
David A. Bluemke, Constantine A. Gatsonis, Mei Hsiu Chen, Gia A. DeAngelis, Nanette DeBruhl, Steven Harms, Sylvia H. Heywang-Köbrunner, Nola Hylton, Christiane K. Kuhl, Constance Lehman, Etta D. Pisano, Petrina Causer, Stuart J. Schnitt, Stanley F. Smazal, Carol B. Stelling, Paul T. Weatherall, Mitchell D. Schnall. Magnetic Resonance Imaging of the Breast Prior to Biopsy. JAMA. 2004;292(22):2735–2742. doi:10.1001/jama.292.22.2735
Author Affiliations: Russell H. Morgan Department
of Radiology and Radiological Sciences, Johns Hopkins University School of
Medicine, Baltimore, Md (Dr Bluemke); Center for Statistical Sciences, Brown
University, Providence, RI (Dr Gatsonis and Ms Chen); Department of Radiology,
University of Virginia Health System, Charlottesville (Dr DeAngelis); Department
of Radiological Sciences, School of Medine, University of California, Los
Angeles (Dr DeBruhl); Department of Radiology, University of Arkansas for
Medical Sciences, Little Rock (Dr Harms); Department of Breast Imaging, Technical
University, Munich, Germany (Dr Heywang-Köbrunner); Magnetic Resonance
Science Center and Department of Radiology, University of California, San
Francisco (Dr Hylton); Department of Radiology, University of Bonn, Bonn,
Germany (Dr Kuhl); Cancer Care Alliance and Department of Radiology, University
of Washington, Seattle (Dr Lehman); Department of Radiology, University of
North Carolina, Chapel Hill (Dr Pisano); Department of Radiology, University
of Toronto and Sunnybrook Cancer Care Center, Toronto, Ontario (Dr Causer);
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Mass (Dr Schnitt); Radiology Imaging Associates and
Porter Adventist Hospital, Littleton, Colo (Dr Smazal); Division of Diagnostic
Imaging, University of Texas M. D. Anderson Cancer Center, Houston (Dr Stelling);
Department of Radiology, University of Texas Southwestern Medical Center,
Dallas (Dr Weatherall); and the Department of Radiology, University of Pennsylvania,
Philadelphia (Dr Schnall).
Context Breast magnetic resonance imaging (MRI) has been shown to have high
sensitivity for cancer detection and is increasingly used following mammography
to evaluate suspicious breast lesions.
Objective To determine the accuracy of breast MRI in conjunction with mammography
for the detection of breast cancer in patients with suspicious mammographic
or clinical findings.
Design, Setting, and Patients Prospective multicenter investigation of the International Breast MR
Consortium conducted at 14 university hospitals in North America and Europe
from June 2, 1998, through October 31, 2001, of 821 patients referred for
breast biopsy for American College of Radiology category 4 or 5 mammographic
assessment or suspicious clinical or ultrasound finding.
Interventions MRI examinations performed prior to breast biopsy; MRI results were
interpreted at each site, which were blinded to pathological results.
Main Outcome Measures Area under the receiver operating characteristic curve (AUC), sensitivity,
and specificity of breast MRI.
Results Among the 821 patients, there were 404 malignant index lesions, of which
63 were ductal carcinoma in situ (DCIS) and 341 were invasive carcinoma. Of
the 417 nonmalignant index lesions, 366 were benign, 47 showed atypical histology,
and 4 were lobular carcinoma in situ. The AUC pooled over all institutions
was 0.88 (95% confidence interval [CI], 0.86-0.91). MRI correctly detected
cancer in 356 of 404 cancer cases (DCIS or invasive cancer), resulting in
a sensitivity of 88.1% (95% CI, 84.6%-91.1%), and correctly identified as
negative for cancer 281 of 417 cases without cancer, resulting in a specificity
of 67.7% (95% CI, 62.7%-71.9%). MRI performance was not significantly affected
by mammographic breast density, tumor histology, or menopausal status. The
positive predictive values for 356 of 492 patients was 72.4% (95% CI, 68.2%-76.3%)
and of mammography for 367 of 695 patients was 52.8% (95% CI, 49.0%-56.6%)
(P<.005). Dynamic MRI did not improve the AUC
compared with 3-dimensional MRI alone, but the specificity of a washout pattern
for 123 of 136 patients without cancer was 90.4% (95% CI, 84%-95%).
Conclusions Breast MRI has high sensitivity but only moderate specificity independent
of breast density, tumor type, and menopausal status. Although the positive
predictive value of MRI is greater than mammography, MRI does not obviate
the need for subsequent tissue sampling in this setting.
Mammography is the primary imaging modality used to detect clinically
occult breast cancer. However, mammography has limitations in both sensitivity
and specificity that have led to exploration of other imaging techniques.
Magnetic resonance imaging (MRI) has been evaluated for breast imaging because
of its value for assessing soft tissues of the body. Breast MRI is performed
before and after injection of a gadolinium-based contrast agent.1,2 Additional
lesions seen by MRI that are not visible on the mammogram have been reported
to be present in between 27% and 37% of patients.3,4
The use of MRI to evaluate women with mammographically or clinically
suspicious breast lesions who are undergoing biopsy has shown high potential,
with the reported sensitivities of MRI for breast cancer from larger single
center studies ranging from 88% to 95%.5- 12 Thus,
there has been considerable enthusiasm for breast MRI and use of the procedure
for Medicare patients increased almost 3-fold between 2001 (3440 examinations)
and 2003 (10 115 examinations).13 However,
the reported specificity of MRI is variable, ranging from 30% to 80%.5,6,8,10,14,15 Interpretation
of MRI is complicated by 2 fundamentally different methods for performing
breast MRI that are currently used. These 2 methods characterize lesions as
malignant based on 3-dimensional MRI to assess lesion morphology or dynamic
MRI after bolus injection of gadolinium contrast to assess lesion enhancement.16 The optimal imaging method (3-dimensional MRI or
dynamic MRI) remains controversial and has not been subject to evaluation
in large-scale trials.
To address the overall performance of 3-dimensional and dynamic MRI
as an adjunct to conventional methods for breast cancer detection, the National
Cancer Institute sponsored a multicenter clinical study with the aim of defining
the role of MRI for breast cancer evaluation.17 The
purpose of this article is to describe the results of the International Breast
Magnetic Resonance Consortium study that assessed the accuracy of 3-dimensional
MRI and dynamic MRI in patients with mammographically or clinically suspicious
Women self-classified in all races and ethnic groups between the ages
of 18 and 80 years were eligible for the study. Patients were eligible for
enrollment if they were referred for breast biopsy because a mammogram was
classified as American College of Radiology (ACR) category 4 or 5 (suspicious
abnormality, highly suggestive of malignancy, respectively) or if the patient
had a suspicious clinical or ultrasound finding without associated benign
mammographic features. All patients were required to have a mammogram within
2 months of the MRI examination. An index lesion was
defined as the palpable, ultrasonographic or mammographic lesion that was
the basis for the referral for breast biopsy. Patients were enrolled at 1
of 14 university centers in North America and Europe that had documented experience
in breast MRI.
Patients were excluded if (1) a prior excisional or core biopsy of the
affected breast was performed less than 6 months before enrollment, (2) there
was a contraindication to MRI (eg, pacemaker, ferromagnetic aneurysm clip),
(3) there was prior breast cancer in the affected breast, or (4) the patient
was pregnant. The institutional review board at each participating site approved
the study. Written informed consent was obtained from patients prior to any
Mammograms were performed in accordance with ACR standards, and consisted
of craniocaudal and mediolateral oblique views. Spot views with magnification
were performed as needed.
Mammograms were prospectively interpreted with knowledge of the original
clinical findings but without knowledge of pathologic or MRI findings. Mammograms
were coded using the ordered categories of the ACR breast imaging reporting
and data system (BI-RADS) lexicon (category 1, negative; 2, benign finding;
3, probably benign; 4, suspicious finding; 5, highly suggestive of malignancy).
All women underwent high resolution 3-dimensional MRI of the breast
to assess the suspicious lesion. Patients with enhancing abnormalities were
asked to return for dynamic MRI no sooner than 18 hours later. All MRI examinations
were performed at 1.5 T using a dedicated breast coil. A single breast was
imaged to maximize the spatial resolution of the MRI.
High-Resolution 3-Dimensional MRI. T2-weighted
images (slice thickness ≤4 mm and time to repetition of 4000 milliseconds
and time to echo of 90 milliseconds) were obtained to identify cystic breast
lesions. This was followed by a 3-dimensional T1-weighted set of images taken
immediately prior to and after the intravenous administration of 0.1 mmol/kg
of gadolinium chelate.18,19 The
gadolinium chelate was injected over 10 seconds through a 20- or 22-gauge
intravenous catheter followed by a 20-mL saline flush. Imaging began after
gadolinium injection but before the saline flush. The 3-dimensional T1-weighted
parameters were time to repetition of 20 milliseconds or less, time to echo
of 4.5 milliseconds or less, and flip angle of 45°. Chemical shift fat
suppression was used. The field of view was 16 to 18 cm. The image matrix
was greater than or equal to 256 × 128 and the slice thickness
was 3 mm or less. Total imaging time was less than 4 minutes for the 3-dimensional
Dynamic MRI. Patients with focal abnormalities
on 3-dimensional MRI were asked to return for a dynamic MRI with an additional
injection of gadolinium contrast. Two-dimensional, T1-weighted images centered
on the focal abnormality were acquired at 15-second intervals after the administration
of 0.1 mmol/kg of gadolinium chelate administered over 10 seconds, followed
by a 20-mL saline flush. Imaging began at the same time as the gadolinium
injection. Imaging parameters were time to repetition of 100 milliseconds,
time to echo of 4 to 5 milliseconds, and flip angle of 90°. The image
acquisition matrix was 256 × 128 and the slice thickness was
4 mm. Dynamic images were repeatedly acquired every 15 seconds for a total
duration of 5 minutes.
A single reader at each site prospectively interpreted the MRI and was
blinded to the pathological findings. The likelihood of malignancy was classified
as definitely benign (category 1), probably benign (category 2), indeterminate
(category 3), probably malignant (category 4), or definitely malignant (category
5). Enhancement of the lesion on 3-dimensional MRI was classified as malignant
if there was a focal mass with irregular or spiculated margins, if enhancement
was in a ductal distribution, if a solid lesion showed rim enhancement, or
if there was intense regional enhancement in less than 1 quadrant. Enhancement
of the lesion was classified as benign if a focal mass showed smooth or lobulated
margins with internal septations, or if the mass was cystic. Breast lesions
not fitting criteria of either malignant or benign were considered indeterminate.
For dynamic MRI, lesion enhancement was classified by the reader as
a washout, plateau, delayed, or indeterminate enhancement curve.15 The
likelihood of malignancy was also classified by the MRI reader on a 5-category
scale, as described earlier.
Pathology reports and representative slides from core needle biopsies
and excision specimens were sent to a reference pathologist for confirmation
of the final diagnosis. Specimens were classified as benign, atypical, in
situ cancer, or invasive cancer. Patients with negative needle biopsies that
did not yield specific benign diagnoses (eg, fibroadenoma, papilloma) and
who did not undergo subsequent excisional biopsy underwent clinical and mammographic
follow-up after 1 year to ensure stability of the suspicious lesion.
The primary measure of diagnostic performance in the analysis was the
area under the receiver operating characteristic curve (AUC). The receiver
operating characteristic curves and their corresponding AUCs were estimated
using a binormal model for categorical data.20,21 The
comparison of AUC estimates took into account correlations when necessary.
The results of the primary receiver operating characteristic curve analysis
using the binormal model were compared and corroborated using a U statistic, nonparametric approach.22 For
expository purposes, a secondary analysis was conducted in which test results
were treated as binary and estimates of sensitivity, specificity, and predictive
value were derived. For this analysis, MRI and mammography results in categories
1 through 3 were classified as negative and results in categories 4 or 5 were
classified as positive for malignancy. Invasive cancer or ductal carcinoma
in situ (DCIS) were classified as malignant; all others were not malignant.
In a secondary analysis, only invasive cancers comprised the malignant category.
Exact confidence intervals (CIs) were computed for dichotomized test performance.
Correlations were taken into account in the comparisons of positive predictive
values estimated from paired test data.23 All
analyses of diagnostic performance were based on data pooled across sites.
Variation across sites was assessed using hierarchical models,24 fitted
with the WinBUGS software.25
There were 1004 women who met all eligibility criteria enrolled at 1
of 14 enrolling institutions from June 2, 1998, through October 31, 2001 (Figure 1). A total of 821 women (81.8%) had complete
MRI examinations and had a histopathologic reference standard test. The basis
for entry into the trial was an abnormal mammogram in 695 (84.7%) of 821 patients,
a palpable breast abnormality without a lesion on the mammogram in 96 (11.7%)
of 821 patients, an abnormal ultrasound without a lesion on the mammogram
in 15 (1.8%) of 821 patients and other physical examination findings (eg,
nipple discharge) in 15 (1.8%) of 821 patients. There were no significant
differences in demographic or clinical characteristics between eligible patients
and patients who completed the MRI examination and histopathologic reference
standard test (Table 1).
There were 404 malignant index lesions, of which 63 (15.6%) were DCIS
and 341 (84.4%) were invasive carcinoma. Of the remaining index lesions, 366
(98.8%) of 417 were benign, 47 (11.3%) of 417 showed atypical histology, and
4 (1.0%) 417 were lobular carcinoma in situ. A total of 117 patients with
benign tissue by core needle biopsy had follow-up clinical and mammographic
examination at 1 year. All cases confirmed the original core needle biopsy
diagnosis of benign tissue.
Of 821 patients who completed the MRI, 491 (59.8%) had a mammographic
ACR BI-RADS category 4 (suspicious abnormality) index lesion and 204 (24.8%)
had a category 5 (highly suggestive of malignancy) index lesion. The remainder
of the patients had lesions that were clinically suspicious (eg, palpable)
but had mammograms that had benign findings (42/821; 5.1%), no findings (59/821;
7.2%), or no reported results (25/821; 3.1%). Of 695 patients with a mammogram
positive for maligancy (BI-RADS category 4 or 5), 367 patients had DCIS or
invasive cancer, resulting in a positive predictive value for mammography
of 52.8% (95% CI, 49.0%-56.6%). There was no significant difference in frequency
of ACR BI-RADS category or positive predictive value in the eligible patients
compared with the patients who completed the MRI.
Of 404 patients with DCIS or invasive carcinoma, MRI identified 356
as malignant, resulting in a sensitivity of 88.1% (95% CI, 84.6%-91.1%). Of
417 patients without DCIS or invasive cancer, MRI was negative for maligancy
in 281, resulting in a specificity of 67.4% (95% CI, 62.7%-71.9%) (Table 2). Of 492 patients with a positive MRI
for malignancy, 356 patients had DCIS or invasive cancer, resulting in a positive
predictive value of 72.4% (95% CI, 68.2%-76.3%), which was significantly higher
than that of mammography (P<.005). Of 329 patients
with a negative MRI for malignancy, 281 patients had no evidence of DCIS or
invasive cancer, resulting in a negative predictive value of 85.4% (95% CI,
81.1%-89.0%). The AUC was 0.88 (95% CI, 0.86-0.91; Figure 2). There was no significant difference in the AUC for patients
with mammographically detected microcalcifications compared with those without
Ductal carcinoma in situ was identified by MRI in 46 of these 63 patients,
resulting in a sensitivity of 73% (95% CI, 60.3%-83.4%). Of 341 patients with
invasive cancer, MRI identified cancer in 309, resulting in a sensitivity
of 90.9% (95% CI, 87.3%-93.7%). The AUC for invasive tumors (0.91; 95% CI,
0.89-0.93) was greater than that of DCIS (0.76; 95% CI, 0.68-0.83).
The mean (SD) size of malignant lesions was 23 (17) mm. The sensitivity
of MRI as a function of tumor size is shown in Table 3 for both DCIS and invasive cancer. The detection rates by
tumor size show higher detection rates for invasive tumor compared with DCIS
but the 95% CIs overlap because of the small number of DCIS lesions for each
size category. Overall, the sensitivity, AUC, and positive predictive value
of MRI for invasive cancer was significantly greater than that for DCIS (Table 4).
Figure 3 shows receiver operating
characteristic curves for MRI as a function of breast density. Sensitivity
was greatest in patients with mostly fat (90.7%) or scattered fibroglandular
tissue (90.8%) and was least in patients with heterogeneous (86.4%) or dense
breasts (86.5%) (Table 2). However,
differences in sensitivity and AUC between groups were not statistically significant
(all P values >.14).
Of 821 patients, 345 (42.0%) had dynamic MRI of a focal lesion that
was detected by 3-dimensional MRI (Table 5).
There were no significant differences in demographic characteristics between
the group who received dynamic MRI and the group who received 3-dimensional
MRI alone. However, 209 (60.6%) of 345 patients who had dynamic MRI had DCIS
or invasive cancer compared with 404 (49.2%) of 821 patients who had 3-dimensional
Table 5 shows the dynamic MRI
enhancement pattern for malignant and benign lesions. A washout curve was
present in 43 of 209 patients with DCIS or invasive cancer, resulting in a
sensitivity of 20.5% (95% CI, 15%-27%). A washout curve was absent in 123
of 136 patients without DCIS or invasive carcinoma, resulting in a specificity
of 90.4% (95% CI, 84%-95%). A plateau curve was present in 89 of 203 patients
with DCIS or invasive cancer, resulting in a sensitivity of 42.6% (95% CI,
36%-50%). A plateau curve was absent in 102 of 136 patients without DCIS or
invasive cancer, resulting in a specificity of 75% (95% CI, 67%-82%). Using
either plateau or washout curve as an indicator of malignancy yielded a sensitivity
of 63.2% (95% CI, 56.2%-69.7%) and a specificity of 65.4% (95% CI, 56.8%-73.4%).
The sensitivity and specificity of a persistent enhancement curve to indicate
a benign lesion were 52.2% (95% CI, 43%-61%) and 71% (95% CI, 64%-77%), respectively.
The overall interpretation of dynamic MRI data was also classified by
readers for receiver operating characteristic curve analysis. The AUC for
dynamic MRI alone was 0.73 (95% CI, 0.67-0.78). This was significantly less
than the AUC for 3-dimensional MRI (P<.001).
Dynamic and 3-dimensional MRI results were combined by using the higher
of the 2 interpretations as the final score. The AUC for this combined score
was 0.86 (95% CI, 0.82-0.86). The combined score was not significantly different
than the AUC obtained from 3-dimensional MRI alone. By using the lower of
the 2 interpretation scores as the final score, the AUC decreased to 0.76
(95% CI, 0.71-0.81).
Hierarchical model-based estimates of the AUC for each institution ranged
from 0.78 (SE, 0.03) to 0.91 (SE, 0.02). Variation between sites was not significantly
related to the following characteristics: prevalence of malignant disease,
breast density, palpability of breast tumors, or breast calcifications. The
average tumor size showed a trend toward significance, with increasing tumor
size modestly correlating with increased AUC.
This article describes the performance of MRI in conjunction with mammography
in the largest multicenter study to date (821 patients). For patients with
suspicious lesions identified prior to planned breast biopsy, breast MRI has
high accuracy as measured by the AUC of 0.88. The overall sensitivity of MRI
was high (88.1%), but the specificity was only moderate (67.4%). The positive
predictive value for malignancy for MRI (72.4%) was significantly higher than
that of mammography (52.8%). The use of dynamic MRI did not improve the AUC
compared with high resolution 3-dimensional MRI alone.
The overall sensitivity of MRI in this 14-site investigation was within
the range reported for large, single-center studies (range, 88%-95%),5- 10,14,15 albeit
at the lower end of the spectrum. A multicenter study of 463 patients reported
a sensitivity of 86% to 97% depending on the interpretation criteria that
were used.26 We detected a trend toward improved
MRI performance at centers that evaluated larger breast lesions, but other
measures of patient selection criteria showed no significant relationship
to MRI performance. Taken as a whole, however, there is consistent evidence
that breast MRI sensitivity is high, and that results from multicenter studies
are generally consistent with prior single-center data.
The specificity of MRI that has been reported in the literature varies
widely (range, 30%-83%).5,6,8,10,14,15,26 Our
results indicate that the specificity of MRI is only moderate (67.4%). To
improve specificity, radiologists rely on either lesion morphology (eg, irregular
compared smooth lesion borders) using 3-dimensional MRI12,27- 30 and/or
the rate and extent of lesion enhancement depicted by dynamic MRI.2,15,31- 35 This
study provides important insight to the relative importance of dynamic compared
with high resolution 3-dimensional MRI. The dynamic MRI has potential in some
situations to improve specificity; in particular a washout curve was associated
with a specificity of 90.4%. Other patterns of the dynamic enhancement curves
had substantially lower specificity than the washout pattern. Further analysis
of dynamic MRI for certain lesion types or quantitation of enhancement curves
may lead to further methods to improve specificity.26,31 These
approaches are under investigation.
There appears to be no major effect of breast density on the performance
of MRI for patients with ACR BI-RADS 1, 2, or 3 mammograms. For extremely
dense breasts, MRI sensitivity as well as AUC were slightly lower but not
significantly different than the other ACR BI-RADS density categories. The
corresponding sensitivity of mammography was not determined in this study
(because the entrance criteria was an abnormal mammogram, the number of falsely
negative mammograms was not known), but mammography sensitivity has been well
documented previously. Mammography has previously been shown to have decreased
sensitivity in patients with dense breast tissue36 while
cancer risk increases with increasing breast density.37 Bird
et al38 reported that 77 (24%) of 320 cancerous
tumors were missed primarily due to dense breast tissue obscuring an underlying
lesion. Leconte et al39 reported a study of
4236 patients showing mammogram detection rates were 80% for patients with
ACR BI-RADS densities of 1 (mostly fat) or 2 (scattered fibroglandular tissue),
but only 56% for densities of 3 (heterogeneously dense) or 4 (extremely dense).
MRI performance was also independent of menopausal status and tumor histology.
These factors support a role for MRI in breast cancer detection in patients
with mammographically dense breasts. Indeed, studies of patients at high risk
for breast cancer, who are frequently younger and have dense breast tissue,
have shown that MRI detects cancer that is mammographically occult.40
The purpose of this study was to determine breast MRI performance as
an adjunct to mammography. As such, a direct comparison of mammography and
MRI was not performed because the mammography results were used as enrollment
criteria. Some comparisons of the 2 modalities, however, are available within
the study design. For example, MRI had a significantly higher positive predictive
value (72.4%) than mammography (52.8%). Although MRI performance exceeded
mammography in this regard, these findings are balanced by a negative predictive
value of MRI of 85.4%. This negative predictive value is not sufficiently
high in most circumstances to use MRI as an alternative to proceeding directly
to breast biopsy for suspicious lesions.16 Other
various roles of breast MRI such as determining lesion extent, identifying
additional lesions,3,4 or evaluating
the postoperative or scarred breast41 remain
There are several limitations to this study. The positive predictive
value of mammography was relatively high (52.8%) compared with reported values
in the literature of 15% to 30%.42,43 This
suggests that patients with more advanced breast lesions were referred into
the trial. Assessments of the effects of patient characteristics (such as
breast density) were not the primary aim of the study, and subsequent studies
will be needed to confirm these findings. Finally, despite initial training
and interpretation guidelines that were used in the trial as well as selection
of participating sites on the basis of experience with breast MRI, there was
variability in AUC at the 14 participating institutions. These results point
to the importance of multicenter trials to develop true estimates of the performance
of new imaging technologists compared with single-center studies.
In conclusion, MRI shows high sensitivity and moderate specificity for
breast cancer. However, for lesions that are mammographically or clinically
suspicious, tissue sampling of the breast may not be avoided with the use
of MRI. Because MRI appears to be only mildly affected by breast density,
a role for MRI in evaluating patients with dense breast tissue is suggested.
Corresponding Author: David A. Bluemke,
MD, PhD, Department of Radiology, Johns Hopkins Hospital, 600 N Wolfe St,
Baltimore, MD 21287 (email@example.com).
Author Contributions: Dr Schnall 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: Gatsonis, DeAngelis,
Acquisition of data: Bluemke, Gatsonis, DeAngelis,
DeBruhl, Harms, Heywang-Köbrunner, Hylton, Kuhl, Lehman, Pisano, Schnitt,
Smazal, Stelling, Weatherall, Schnall.
Analysis and interpretation of data: Bluemke,
Gatsonis, Chen, Lehman, Pisano, Causer, Schnitt, Weatherall, Schnall.
Drafting of the manuscript: Bluemke, Gatsonis,
DeAngelis, Schnitt, Schnall.
Critical revision of the manuscript for important
intellectual content: Bluemke, Gatsonis, Chen, DeAngelis, DeBruhl,
Harms, Heywang-Köbrunner, Hylton, Kuhl, Lehman, Pisano, Causer, Schnitt,
Smazal, Stelling, Weatherall, Schnall.
Statistical analysis: Gatsonis, Chen.
Obtained funding: Gatsonis, Schnall.
Administrative, technical, or material support:
Bluemke, Gatsonis, DeAngelis, Harms, Hylton, Kuhl, Lehman, Pisano, Causer,
Smazal, Weatherall, Schnall.
Study supervision: Bluemke, Gatsonis, DeAngelis,
Heywang-Köbrunner, Weatherall, Schnall.
Financial Disclosure: Dr Weatherall has received
a research grant from Philips Medical Systems. Dr Schnall has received a research
grant from Siemens Medical Systems and has a royalty agreement with USA Instruments.
Funding/Support: This study was funded by grants
UO1-CA74696 and UO1-CA74680 from the National Cancer Institute. Gadolinium
contrast agents were provided by Amersham Health, Berlex Laboratories, and
Role of the Sponsor: The National Cancer Institute’s
project officer had input into the study design and monitored ongoing study
progress including recruitment rates. No other sponsor had any role in the
study design, conduct, collection, management, analysis, or intrepretation
of the data, or preparation, review, or approval of the manuscript.
Acknowledgment: We thank Paul Stomper, MD,
of Roswell Park Cancer Center and Carl D’Orsi, MD, of the Emory Clinic
for central review of mammograms.