Skip Navigation
Department of Health and Human Services www.hhs.gov
  • Home
  • Search for Research Summaries, Reviews, and Reports
 
 

EHC Component

  • EPC Project

Topic Title

  • Noninvasive Diagnostic Tests for Breast Abnormalities: Update of a 2006 Review

Full Report

Related Products for this Topic

Related Links for this Topic

Save this page in Facebook.com  Save this page in Myspace.com  Save this page in Twitter.com  Save this page on your Google Home Page  Save this page in Windows Live
Save this page in Yahoo  Save this page in Ask.com  Stumble this page.  Save this page in del.ico.us  Digg this page. 

E-mail E-mail   Print Print

Add to My Collections



Executive Summary – Feb. 13, 2012

Noninvasive Diagnostic Tests for Breast Abnormalities: Update of a 2006 Review

Formats

Current: This report was assessed in January 2013 and conclusions were considered current.

Table of Contents

Background

Breast cancer is one of the most common malignancies of women, with approximately 200,000 new cases diagnosed every year in the United States.1 Some breast cancers are identified by physical examination (either self-examination or an examination performed by a physician). Population-wide screening programs that use x-ray mammography to examine asymptomatic women for early signs of breast cancer are also in common use.2-4 If a suspicious area is seen on x-ray mammography, women are usually recalled for further examination. The results of these examinations are used to make decisions about further management: return to normal screening/return for short-interval followup/refer for biopsy. In current standard practice the examinations conducted after recall usually consist of diagnostic mammography and possibly ultrasound. More and more often women are being sent for additional imaging during recall workup. Extensive diagnostic ultrasound examinations and MRI are currently the most commonly chosen additional imaging added to the workup, but other imaging technologies are offered by some practitioners.

It is important to triage recalled women into the correct management pathway. Women with readily treatable early-stage cancers who get mistakenly triaged into “return to normal screening” may experience a significant delay in diagnosis and treatment of the cancer. However, the majority of women who are recalled for further assessment after a screening mammography do not have cancer, and significant numbers of healthy women are referred for biopsy or short-interval followup after recall and diagnostic mammography.5,6

A number of noninvasive imaging technologies have been developed and proposed to be useful as part of the workup after recall. This evidence review focuses on additional noninvasive imaging studies that can be conducted (in addition to standard workup) after discovery of a possible abnormality on screening mammography or physical examination. These studies are intended to guide patient management decisions. In other words, these imaging studies are not intended to provide a final diagnosis as to the nature of the breast lesion; rather, they are intended to provide additional information about the nature of the lesions such that women can be more appropriately triaged into the correct management pathway. It is important to evaluate the evidence to see if women do or do not benefit from the addition of these imaging modalities to the standard workup after recall on breast cancer screening.

Because there are no available studies that directly evaluate whether women benefit from additional imaging in this context, we addressed this important question indirectly. First we evaluated the accuracy of the imaging tests in distinguishing between “benign” and “malignant” breast lesions. Inaccurate tests will lead to suboptimal management decisions and less than desirable patient outcomes. The accuracy of the noninvasive imaging tests was primarily measured in terms of sensitivity and specificity. Sensitivity is a measure of how accurately the test can identify women with cancer; specificity is a measure of how accurately the test can identify women who do not have cancer. A test with high sensitivity will rarely misclassify women with cancer as not having cancer, and a test with high specificity will rarely misclassify women without cancer as having cancer.

The accuracy of a test can also be expressed in a more clinically useful measure, namely, likelihood ratios. When making medical decisions, a clinician can use likelihood ratios and test results to estimate the probability of an individual woman having breast cancer. Clinicians use individual patient characteristics (such as age and family history) and features seen on the diagnostic mammogram (such as microcalcifications or distortions) to estimate a woman’s risk of malignancy. This estimate is known as a “pre-test” or “prior” probability. The clinician can then use the likelihood ratios (that express the accuracy of the test) to decide if an additional imaging test will be helpful in guiding management decisions. For example, if a clinician estimates a woman’s risk of malignancy as greater than 50 percent, most likely the use of any additional imaging test, even a very accurate imaging test, will not change the clinician’s management recommendation of a biopsy, and therefore additional imaging will not be beneficial to the woman. However, if a clinician estimates a woman’s risk of malignancy as being uncertain or close to a clinical threshold (2%), the likelihood ratios can be used to estimate whether the results of an additional test are likely to change management decisions and possibly affect patient outcomes.

After establishing the accuracy of the various imaging tests, we used the summary likelihood ratios to prepare simple models of various clinical scenarios. In doing so, we attempted to indirectly address the implicit question of whether women benefit from the addition of noninvasive imaging tests to standard workup after recall for evaluation of a possible breast abnormality detected by screening mammography or physical examination.

This report is an update of a Comparative Effectiveness Review (CER) of the same title originally published in 2006.7 In addition to an update of the literature, the Key Questions have been revised and additional noninvasive imaging tests have been added.

Methods

Topic Development and Scope

The topic was selected for update by the Effective Health Care program. The Key Questions were posted for public comment. A Technical Expert Panel was assembled to provide expert input, and a protocol for updating the review was developed by the EPC authors and approved by the Agency for Healthcare Research and Quality.

Patient Population

The patient population of interest is the general population of women participating in routine breast cancer screening programs (including mammography, clinical examination, and self-examination) who have been recalled after discovery of a possible abnormality and who have already undergone standard workup (which usually includes diagnostic mammography and/or ultrasound) . In other words, the patient population of interest consists of women who have or might receive a Breast Imaging-Reporting and Data System (BI-RADS®) rating of 0, or 3 to 5, after standard workup. Some of the women evaluated may have had an ultrasound examination before being examined using the technology under study, including the women being evaluated by diagnostic ultrasound. Although not explicitly stated in the studies, in most cases this prior ultrasound seemed to be used primarily to identify women with simple benign cysts, who were then not included in the study. Populations that were not evaluated in this review include: women thought to be at very high risk of breast cancer due to family history or breast cancer (BRCA) gene mutations; women with a personal history of breast cancer; women presenting with overt symptoms (such as pain or nipple discharge); and men.

Interventions

The noninvasive diagnostic tests evaluated were ultrasound (conventional B mode grayscale, harmonic, tomography, color Doppler, and power Doppler); magnetic resonance imaging (MRI, with gadolinium-based contrast agents) with or without computer-aided diagnosis (CADx); positron emission tomography (PET, with 18-fluorodeoxyglucose [FDG]), with or without concurrent computed tomography (CT) scans (including positron emission mammography [PEM]); scintimammography (with technetium-99m sestamibi [MIBI]), including Breast Specific Gamma Imaging (BSGI).

Comparators

The accuracy of the noninvasive diagnostic tests were evaluated by a direct comparison with histopathology (surgical or biopsy specimens) or with clinical followup, or a combination of these methods. In addition, the relative accuracy of the different tests under evaluation were directly and indirectly compared as the evidence permitted.

Outcomes

Outcomes of interest are diagnostic test characteristics; namely, sensitivity, specificity, and likelihood ratios. Because predictive values vary as the prevalence of disease changes, we did not calculate predictive values. Adverse events related to the procedures, such as radiation exposure, discomfort, and reactions to contrast agents, were also be discussed as the evidence permitted. Our literature searches did not identify any relevant studies that directly reported the impact of the diagnostic tests on patient-oriented outcomes. Therefore, we used the estimates of accuracy and various clinical scenarios to address the implicit, very important question of whether women benefit from the use of these noninvasive imaging tests.

Timing

Any duration of followup, from same day interventions to many years of clinical followup, were evaluated.

Setting

Any care setting was evaluated, including general hospitals, physician’s offices, and specialized breast imaging centers.

Study Selection

We searched the medical literature, including PubMed and Embase, from December 1994 through September 2010. We included diagnostic cohort studies that enrolled the patient population of interest and used current generation scanners and protocols of the noninvasive imaging technologies of interest. We excluded case-control studies, meeting presentations, and very small (<10 patients) studies. Data were abstracted from the included studies.

Strength of Evidence

We graded the strength of evidence supporting each major conclusion as high, moderate, low, or insufficient. The grade was developed by considering four important domains: the risk of bias in the evidence base (internal validity, or the quality of the studies), the consistency of the findings, the precision of the results, and the directness of the evidence.

Data Analysis

We used a bivariate mixed-effects binomial regression model for meta-analysis of data.8,9 We used summary likelihood ratios and Bayes’ theorem to calculate the post-test probability of having a benign or malignant lesion. In cases where a bivariate binomial model could not be fit, we meta-analyzed the data using two random-effects models, one for sensitivity and one for specificity.10 We explored heterogeneity in the data with meta-regressions using standard methodology.9

Peer Review and Public Commentary

The draft received comments from peer reviewers, and from members of the public through an open public comment period.

Results

Magnetic Resonance Imaging

We identified 41studies of MRI that included a total of 3,882 patients with 4,202 suspicious breast lesions.11-51 We combined the data reported by all 41 studies into a bivariate binomial mixed-effects model. The summary sensitivity was 91.7 percent (95% CI: 88.5 to 94.1%) and the summary specificity was 77.5 percent (95% CI: 71.0 to 82.9%). The estimate of accuracy was judged to be supported by a moderate to low strength of evidence (low for the estimate of specificity due to the wide confidence interval). The dataset was very heterogeneous (I2 = 98.4%). We explored the heterogeneity with meta-regression and found that the prevalence of disease in the study population and whether or not the image readers were blinded was statistically significantly correlated with the results. Subgroup analyses found that MRI was less sensitive for evaluation of microcalcifications (84.0% vs. 91.7% summary sensitivity).

The probability that a woman actually has cancer (invasive or in situ) even after a finding of “benign” on MRI depends on her probability of having cancer before undergoing the test. Bayes’ theorem and the summary likelihood ratios indicate that if a woman with an estimated 5 to 10 percent chance of having cancer undergoes MRI and has a finding of “benign” she will then have an estimated 1 percent chance of having cancer; a woman with an estimated 20 percent chance of having cancer who has a finding of “benign” on MRI will then have an estimated 3 percent chance of having cancer; and a woman with an estimated 50 percent chance of having cancer who has a finding of “benign” on MRI will then have an estimated 10 percent chance of having cancer.

Positron Emission Tomography

We identified seven studies of PET34,35,41,52-55 and one study of PET/CT16 that met our inclusion criteria. The studies of stand-alone PET included 308 women with 403 suspicious breast lesions. We combined the data reported by the seven studies of PET into a bivariate binomial mixed-effects model. The summary sensitivity was 83.0 percent (95% CI: 73.0 to 89.0%) and the summary specificity was 74.0 percent (95% CI: 58.0 to 86.0%). The estimate of accuracy was judged to be supported by a Low strength of evidence. The dataset contained moderate heterogeneity (I2 = 64.0%). We explored the heterogeneity with meta-regression and did not identify any possible causes. Subgroup analyses found that PET was more sensitive for evaluation of palpable lesions.

The probability that a woman actually does have cancer (invasive or in situ) even after a finding of “benign” on PET depends on her probability of having cancer before undergoing the test. Bayes’ theorem and the summary likelihood ratios indicate that if a woman with an estimated 5 percent chance of having cancer undergoes PET and has a finding of “benign” she will then have an estimated 1 percent chance of having cancer; a woman with an estimated 20 percent chance of having cancer who has a finding of “benign” on PET will then have an estimated 6 percent chance of having cancer; and a woman with an estimated 50 percent chance of having cancer who has a finding of “benign” on PET will then have an estimated 19 percent chance of having cancer.

Scintimammography

We identified 10 studies of scintimammography14,56-64 and one study of BSGI19 that met our inclusion criteria. The studies included a total of 1,064 suspicious lesions. We combined the data reported by all 11 studies into a bivariate binomial mixed-effects model. The summary sensitivity was 84.7 percent (95% CI: 78.0 to 89.7%) and the summary specificity was 77.0 percent (95% CI: 64.7 to 85.9%). The estimate of accuracy was judged to be supported by a low strength of evidence. The dataset was very heterogeneous (I2 = 93.0%). We explored the heterogeneity with meta-regression and did not identify any possible causes.

The probability that a woman actually does have cancer (invasive or in situ) even after a finding of “benign” on scintimammography depends on her probability of having cancer before undergoing the test. Bayes’ theorem and the summary likelihood ratios indicate that if a woman with an estimated 5 percent chance of having cancer undergoes scintimammography and has a finding of “benign” she will then have an estimated 1 percent chance of having cancer; a woman with an estimated 20 percent chance of having cancer who has a finding of “benign” on scintimammography will then have an estimated 5 percent chance of having cancer; and a woman with an estimated 50 percent chance of having cancer who has a finding of “benign” on scintimammography will then have an estimated 17 percent chance of having cancer.

Ultrasound

We identified a total of 31 diagnostic cohort studies of ultrasound. Of these, there were 21 studies of B-mode grayscale ultrasound,18,26,65-83 six studies of color Doppler ultrasound,78,80,84-87 and nine studies of power Doppler ultrasound.65,72,75,77,86,88-91 We combined the data reported by these studies into bivariate binomial mixed-effects models. For B-mode grayscale, summary sensitivity was 92.4 percent (95% CI: 84.6 to 96.4%) and the summary specificity was 75.8 percent (95% CI: 60.8 to 86.3%); for color Doppler, summary sensitivity was 88.5 percent (95% CI: 74.4 to 95.4%) and summary specificity was 76.4 percent (95% CI: 61.7 to 86.7%); for power Doppler, summary sensitivity was 70.8 percent (95% CI: 47 to 86.6%) and summary specificity was 72.6 percent (95% CI: 59.9 to 82.5%). These estimates of accuracy were all judged to be supported by a low strength of evidence. The datasets were heterogeneous. We explored the heterogeneity of the largest dataset (21 studies of B-mode) with meta-regression and found that whether the studies blinded the image readers and accounted for inter-reader differences were statistically significantly associated with the results.

The probability that a woman actually does have cancer (invasive or in situ) even after a finding of “benign” on ultrasound depends on her probability of having cancer before undergoing the test. Bayes’ theorem and the summary likelihood ratios indicate that if a woman with an estimated 5 to 10 percent chance of having cancer undergoes B-mode grayscale ultrasound and has a finding of “benign” she will then have an estimated 1 percent chance of having cancer; a woman with an estimated 20 percent chance of having cancer who has a finding of “benign” on B-mode grayscale ultrasound will then have an estimated 2 percent chance of having cancer; and a woman with an estimated 50 percent chance of having cancer who has a finding of “benign” on B-mode grayscale ultrasound will then have an estimated 9 percent chance of having cancer.

Discussion

According to the American College of Radiology, the threshold of suspicion of malignancy at which management of women changes is 2 percent.92 After recall and workup, women with a suspicion of malignancy greater than 2 percent are generally recommended to undergo tissue sampling of some kind (biopsy), and women with a lower suspicion of malignancy are triaged into imaging management pathways (short-interval followup or return to regular screening). We used the 2 percent threshold to explore the clinical usefulness of the various noninvasive imaging technologies as add-ons to the current standard of care; namely, if a woman was recalled for evaluation after a screening mammography, and received standard-of-care workup versus standard-of-care workup plus the noninvasive imaging technology, would use of the noninvasive imaging technology be likely to alter the recommendations for care after the workup?

For all of the technologies evaluated in this assessment, only women with a low suspicion of malignancy after standard-of-care workup might be expected to experience a change in management decisions as a result of additional noninvasive imaging. A woman with a ≤12 percent suspicion of malignancy who has benign findings on MRI could have her suspicion of malignancy drop below the 2 percent threshold, and therefore she might be assigned to short-interval imaging followup management rather than tissue sampling management; a woman with a 1 percent suspicion of malignancy who has benign findings on MRI could have her suspicion of malignancy drop to near 0 percent and therefore she might be assigned to return to normal screening rather than short-interval followup imaging; a woman with a 1 percent suspicion of malignancy who has malignant findings on MRI could have her suspicion of malignancy increase to 4 percent and therefore she might be assigned to tissue sampling management rather than short-interval followup. The equivalent thresholds of pre-test suspicion of malignancy at which additional imaging may change management are: for B-mode grayscale ultrasound, 1 to 10 percent; for scintimammography, 1 to 5 percent; and for PET, 1 to 5 percent.

Therefore, if the 2 percent threshold is chosen, the use of noninvasive imaging in addition to standard workup may be clinically useful for diagnostic purposes only for women with a low suspicion of malignancy. When choosing which noninvasive imaging technology to use for this purpose, diagnostic B mode grayscale ultrasound and MRI appear to be more accurate than PET, scintimammography, or the other types of ultrasound (e.g., Doppler) that were evaluated in this comparative effectiveness review.

Women thought to be at moderate to high risk of malignancy after standard workup will not have their estimate of risk of malignancy change sufficiently after further noninvasive imaging to affect management decisions. For many patients the suspicion of malignancy will not be able to be estimated with sufficient precision for clinicians to feel comfortable recommending return to normal screening (rather than a biopsy or short-interval followup) solely on the basis of additional noninvasive imaging. Estimates of risk of malignancy are based on features of the mammographic images, patient characteristics, patient history, and patient family history. Several of our expert reviewers did not think such precise estimation of risk is feasible using currently available methods. Potential harms of noninvasive imaging, such as radiation exposure, also need to be considered when deciding whether to perform these tests.

Changes Since 2006

This CER is an update of a CER finalized in 2006.7 The updated results are, in general, very similar to the findings of the 2006 report. For MRI, in 2006 we found that the sensitivity was 92.5 percent and the specificity was 75.5 percent; the updated evidence base supported estimates of 91.7 percent sensitivity and 77.5 percent specificity. In both reports, MRI was found to be less sensitive (approximately 85%) for evaluation of microcalcifications than for evaluation of lesions in general. For PET, in 2006 we found that the sensitivity was 82.2 percent and the specificity was 78.3 percent; the updated evidence base supported estimates of 83.0 percent sensitivity and 74.0 percent specificity. In the updated report we attempted to evaluate the accuracy of PET/CT, but only one study that met the inclusion criteria was identified.

For scintimammography, the updated evidence base identified a sensitivity of 84.7 percent, much higher than the sensitivity estimate from 2006 of 68.7 percent. Specificity was estimated at 84.8 percent in 2006, and at 77.0 percent in the update; however, the confidence intervals around the updated estimate of specificity are wide. It is possible that improvements in the technology in the last few years improved the sensitivity of the technique.

For ultrasound, in 2006 we evaluated a relatively small set of studies of B-mode grayscale ultrasound, and estimated a sensitivity of 86.1 percent and a specificity of 66.4 percent. The update included a significantly expanded evidence base on B-mode grayscale ultrasound, and identified a sensitivity of 92.4 percent and specificity of 75.8 percent. In the update we included numerous other types of ultrasound, including power and color Doppler ultrasound, that were not studied in the 2006 report.

Remaining Issues

The conclusions of quantitative accuracy were for the most part rated as being supported by low strength of evidence, due primarily to the imprecision of the estimates (wide confidence intervals around the estimates of accuracy); the publication of additional diagnostic accuracy studies are likely to increase the precision of the estimates of accuracy, which may upgrade the strength of evidence rating. There was also considerable heterogeneity (inconsistency) in the majority of the evidence bases, which contributed to the low strength of evidence rating. Most likely the heterogeneity was due to slight differences in imaging methodology or patient populations across studies; future research intended to tease out factors affecting the accuracy of imaging may be helpful to the clinician when deciding whether a test may be a useful addition to standard workup for management of a particular patient.

However, the publication of additional diagnostic accuracy studies is unlikely to affect the implications of the conclusions. The conclusions of diagnostic accuracy lead indirectly to a conclusion that only women with a low (1 to 12%) suspicion of malignancy will experience a “change in management” (which may or may not be beneficial) from the use of these noninvasive diagnostic tests. Improving the precision of the estimates of accuracy or upgrading the strength of evidence rating in response to the publication of more diagnostic accuracy studies will not affect the indirect conclusion. Studies that address the issue of how to establish more accurate estimates of malignancy from diagnostic mammography for an individual patient may be more clinically relevant than additional diagnostic accuracy studies.

A limitation of the current evidence base that should be addressed in future research is the patient population being evaluated. Many of the currently available studies were conducted only on women who had been scheduled for biopsy after standard workup, and therefore the patient population studied is not truly representative of the entire patient population of interest. Additional studies that enroll women referred for short-interval followup after standard workup are needed to confirm that the findings of this assessment do apply to the patient population of interest.

In addition, the majority of studies did not report data separately for different categories of breast lesions or patient characteristics. Future research should focus on the accuracy of noninvasive imaging technologies for discrete categories of lesions, such as nonpalpable lesions classified as BI-RADS 3, or for discrete categories of women, such as women older than age 75. Information from more granular groupings of women will allow estimates of test accuracy to be more immediately clinically useful.

Future research efforts should also focus on studies that report the impact of the use of noninvasive imaging on patient-oriented outcomes such as quality of life, and on evaluation of newer noninvasive imaging technologies.

Conclusions

Our key findings are summarized in Table A. In conclusion, the use of noninvasive imaging in addition to standard workup after recall for evaluation of a breast lesion detected on screening mammography or physical examination may be clinically useful for diagnostic purposes only for women with a low (1 to 12%) suspicion of malignancy. When choosing which noninvasive imaging technology to use for this purpose, diagnostic B-mode grayscale ultrasound and MRI appear to more accurate than PET, scintimammography, or Doppler ultrasound. However, whether these findings are clinically relevant hinges on whether clinicians can identify those women who, after standard workup after recall, have a risk of malignancy in this range. Several expert reviewers of this report expressed doubt about the feasibility of such precise estimation.

Table A. Summary of key findings
Technology Summary Sensitivity Summary Specificity Pretest Probability of Malignancy Thresholda Strength of Evidence
a The threshold at which use of the noninvasive imaging test may change the post-test probability of malignancy sufficiently to trigger a change in patient management.
B-mode grayscale 2D ultrasound 92.4%
(84.6 to 96.4%)
75.8%
(60.8 to 86.3%)
1 to 10% Low
MRI 91.7%
(88.5 to 94.1%)
77.5%
(71.0 to 82.9%)
1 to 12% Moderate (sensitivity) to Low (specificity)
Scintimammography 84.7%
(78.0 to 89.7%)
77.0%
(64.7 to 85.9%)
1 to 5% Low
PET 83.0%
(73.0 to 89.0%)
74.0%
(58.0 to 86%)
1 to 5% Low

References

  1. American Cancer Society (ACS). Cancer facts & figures 2010. Atlanta (GA): American Cancer Society (ACS); 2010. 68 p. www.cancer.org/acs/groups/content/@epidemiologysurveilance/ documents/document/acspc-026238.pdf Exit Disclaimer.
  2. U.S. Preventive Services Task Force (USPSTF). Screening for breast cancer: recommendations and rationale. AHRQ Publication No. APPIP02-507A. Rockville, MD: Agency for Healthcare Research and Quality; February 2002.
  3. Humphrey LL, Helfand M, Chan BK, et al. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002 Sep 3;137(5 Part 1):347-67. PMID: 12204020
  4. U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009 Nov 17;151(10):716-26, W-236. PMID: 19920272
  5. Elmore JG, Barton MB, Moceri VM, et al. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med. 1998 Apr 16;338(16):1089-96. PMID: 9545356
  6. Rosenberg RD, Yankaskas BC, Abraham LA, et al. Performance benchmarks for screening mammography. Radiology. 2006 Oct;241(1):55-66. PMID: 16990671
  7. Bruening W, Launders J, Pinkney N, et al. Effectiveness of noninvasive diagnostic tests for breast abnormalities. Comparative Effectiveness Review No. 2 (Prepared by ECRI Evidence-based Practice center under Contract No. 290-02-0019). AHRQ Publication No. 06-EHC005-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2006. http://effectivehealthcare.ahrq.gov/repFiles/BrCADx%20Final%20Report.pdf.
  8. Harbord RM, Deeks JJ, Egger M, et al. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007 Apr;8(2):239-51. PMID: 16698768
  9. STATA statistics/data analysis. MP parallel edition. College Station (TX): StataCorp; 1984-2007. Single user Stata for Windows. www.stata.com Exit Disclaimer.
  10. Zamora J, Abraira V, Muriel A, et al. Meta DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31. PMID: 16836745
  11. Akita A, Tanimoto A, Jinno H, et al. The clinical value of bilateral breast MR imaging: is it worth performing on patients showing suspicious microcalcifications on mammography? Eur Radiol. 2009 Sep;19(9):2089-96. PMID: 19350244
  12. Baltzer PA, Freiberg C, Beger S, et al. Clinical MR-mammography: are computer-assisted methods superior to visual or manual measurements for curve type analysis? A systematic approach. Acad Radiol. 2009 Sep;16(9):1070-6. PMID: 19523854
  13. Hara M, Watanabe T, Okumura A, et al. Angle between 1 and 4 min gives the most significant difference in time-intensity curves between benign disease and breast cancer: analysis of dynamic magnetic resonance imaging in 103 patients with breast lesions. Clin Imaging. 2009 Sep-Oct;33(5):335-42. PMID: 19712811
  14. Kim IJ, Kim YK, Kim SJ. Detection and prediction of breast cancer using couble phase Tc-99m MIBI scintimammography in comparison with MRI. Onkologie. 2009 Oct;32(10):556-60. PMID: 19816071
  15. Lo GG, Ai V, Chan JK, et al. Diffusion-weighted magnetic resonance imaging of breast lesions: first experiences at 3 T. J Comput Assist Tomogr. 2009 Jan-Feb;33(1):63-9. PMID: 19188787
  16. Imbriaco M, Caprio MG, Limite G, et al. Dual-time-point 18F-FDG PET/CT versus dynamic breast MRI of suspicious breast lesions. AJR Am J Roentgenol. 2008 Nov;191(5):1323-30. PMID: 18941064
  17. Pediconi F, Catalano C, Padula S, et al. Contrast-enhanced MR mammography: improved lesion detection and differentiation with gadobenate dimeglumine. AJR Am J Roentgenol. 2008 Nov;191(5):1339-46. PMID: 18941066
  18. Vassiou K, Kanavou T, Vlychou M, et al. Characterization of breast lesions with CE-MR multimodal morphological and kinetic analysis: comparison with conventional mammography and high-resolution ultrasound. Eur J Radiol. 2009 Apr;70(1):69-76. PMID: 18295425
  19. Brem RF, Petrovitch I, et al. Breast-specific gamma imaging with 99mTc-Sestamibi and magnetic resonance imaging in the diagnosis of breast cancer—a comparative study. Breast J. 2007 Sep-Oct;13(5):465-9. PMID: 17760667
  20. Cilotti A, Iacconi C, Marini C, et al. Contrast-enhanced MR imaging in patients with BI-RADS 3-5 microcalcifications. Radiol Med. 2007 Mar;112(2):272-86. PMID: 17361370
  21. Pediconi F, Catalano C, Padula S, et al. Contrast-enhanced magnetic resonance mammography: does it affect surgical decision-making in patients with breast cancer? Breast Cancer Res Treat. 2007 Nov;106(1):65-74. PMID: 17203383
  22. Zhu J, Kurihara Y, Kanemaki Y, et al. Diagnostic accuracy of high-resolution MRI using a microscopy coil for patients with presumed DCIS following mammography screening. J Magn Reson Imaging. 2007 Jan;25(1):96-103. PMID: 17154376
  23. Bazzocchi M, Zuiani C, Panizza P, et al. Contrast-enhanced breast MRI in patients with suspicious microcalcifications on mammography: results of a multicenter trial. AJR Am J Roentgenol. 2006 Jun;186(6):1723-32. PMID: 16714666
  24. Gokalp G, Topal U. MR imaging in probably benign lesions (BI-RADS category 3) of the breast. Eur J Radiol. 2006 Mar;57(3):436-44. PMID: 16316732
  25. Kneeshaw PJ, Lowry M, Manton D, et al. Differentiation of benign from malignant breast disease associated with screening detected microcalcifications using dynamic contrast enhanced magnetic resonance imaging. Breast. 2006 Feb;15(1):29-38. PMID: 16002292
  26. Ricci P, Cantisani V, Ballesio L, et al. Benign and malignant breast lesions: efficacy of real time contrast-enhanced ultrasound vs. magnetic resonance imaging. Ultraschall Med. 2007 Feb;28(1):57-62. PMID: 17304413
  27. Pediconi F, Catalano C, Venditti F, et al. Color-coded automated signal intensity curves for detection and characterization of breast lesions: preliminary evaluation of a new software package for integrated magnetic resonance-based breast imaging. Invest Radiol. 2005 Jul;40(7):448-57. PMID: 15973137
  28. Pediconi F, Catalano C, Occhiato R, et al. Breast lesion detection and characterization at contrast-enhanced MR mammography: gadobenate dimeglumine versus gadopentetate dimeglumine. Radiology. 2005 Oct;237(1):45-56. PMID: 16126926
  29. Wiener JI, Schilling KJ, Adami C, et al. Assessment of suspected breast cancer by MRI: a prospective clinical trial using a combined kinetic and morphologic analysis. AJR Am J Roentgenol. 2005 Mar;184(3):878-86. PMID: 15728612
  30. Bluemke DA, Gatsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004 Dec 8;292(22):2735-42. PMID: 15585733
  31. Huang W, Fisher PR, Dulaimy K, et al. Detection of breast malignancy: diagnostic MR protocol for improved specificity. Radiology. 2004 Aug;232(2):585-91. PMID: 15205478
  32. Bone B, Wiberg MK, Szabo BK, et al. Comparison of 99mTc-sestamibi scintimammography and dynamic MR imaging as adjuncts to mammography in the diagnosis of breast cancer. Acta Radiol. 2003 Jan;44(1):28-34. PMID: 12630995
  33. Daldrup-Link HE, Kaiser A, Helbich T, et al. Macromolecular contrast medium (feruglose) versus small molecular contrast medium (gadopentetate) enhanced magnetic resonance imaging: differentiation of benign and malignant breast lesions. Acad Radiol. 2003 Nov;10(11):1237-46. PMID: 14626298
  34. Heinisch M, Gallowitsch HJ, Mikosch P, et al. Comparison of FDG-PET and dynamic contrast-enhanced MRI in the evaluation of suggestive breast lesions. Breast. 2003 Feb;12(1):17-22. PMID: 14659351
  35. Walter C, Scheidhauer K, Scharl A, et al. Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions. Eur Radiol. 2003 Jul;13(7):1651-6. PMID: 12835981
  36. Guo Y, Cai YQ, Cai ZL, et al. Differentiation of clinically benign and malignant breast lesions using diffusion-weighted imaging. J Magn Reson Imaging. 2002 Aug;16(2):172-8. PMID: 12203765
  37. Kelcz F, Furman-Haran E, Grobgeld D, et al. Clinical testing of high-spatial-resolution parametric contrast-enhanced MR imaging of the breast. AJR Am J Roentgenol. 2002 Dec;179(6):1485-92. PMID: 12438042
  38. Schedel H, Oellinger H, Kohlschein P, et al. Magnetic Resonance Female Breast Imaging (MRFBI) - evaluation of the changes in signal intensity over time pre- and post-administration of 0.2 mmol/kg Gd-DTPA. Zentralbl Gynakol. 2002 Feb;124(2):104-10. PMID: 11935495
  39. Trecate G, Tess JD, Vergnaghi D, et al. Breast microcalcifications studied with 3D contrast-enhanced high-field magnetic resonance imaging: more accuracy in the diagnosis of breast cancer. Tumori. 2002 May-Jun;88(3):224-33. PMID: 12195761
  40. Kristoffersen Wiberg M, Aspelin P, Perbeck L, et al. Value of MR imaging in clinical evaluation of breast lesions. Acta Radiol. 2002 May;43(3):275-81. PMID: 12100324
  41. Brix G, Henze M, et al. Comparison of pharmacokinetic MRI and [18F] fluorodeoxyglucose PET in the diagnosis of breast cancer: initial experience. Eur Radiol. 2001;11(10):2058-70. PMID: 11702142
  42. Cecil KM, Schnall MD, Siegelman ES, et al. The evaluation of human breast lesions with magnetic resonance imaging and proton magnetic resonance spectroscopy. Breast Cancer Res Treat. 2001 Jul;68(1):45-54. PMID: 11678308
  43. Furman-Haran E, Grobgeld D, Kelcz F, et al. Critical role of spatial resolution in dynamic contrast-enhanced breast MRI. J Magn Reson Imaging. 2001 Jun;13(6):862-7. PMID: 11382945
  44. Imbriaco M, Del Vecchio S, Riccardi A, et al. Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses. Eur J Nucl Med. 2001 Jan;28(1):56-63. PMID: 11202453
  45. Malich A, Boehm T, Facius M, et al. Differentiation of mammographically suspicious lesions: evaluation of breast ultrasound, MRI mammography and electrical impedance scanning as adjunctive technologies in breast cancer detection. Clin Radiol. 2001 Apr;56(4):278-83. PMID: 11286578
  46. Nakahara H, Namba K, Fukami A, et al. Three-dimensional MR imaging of mammographically detected suspicious microcalcifications. Breast Cancer. 2001;8(2):116-24. PMID: 11342984
  47. Torheim G, Godtliebsen F, Axelson D, et al. Feature extraction and classification of dynamic contrast-enhanced T2*-weighted breast image data. IEEE Trans Med Imaging. 2001 Dec;20(12):1293-301. PMID: 11811829
  48. Wedegartner U, Bick U, Wortler K, et al. Differentiation between benign and malignant findings on MR-mammography: usefulness of morphological criteria. Eur Radiol. 2001;11(9):1645-50. PMID: 11511885
  49. Yeung DK, Cheung HS, Tse GM. Human breast lesions: characterization with contrast-enhanced in vivo proton MR spectroscopy—initial results. Radiology. 2001 Jul;220(1):40-6. PMID: 11425970
  50. Kvistad KA, Rydland J, Vainio J, et al. Breast lesions: evaluation with dynamic contrast-enhanced T1-weighted MR imaging and with T2*-weighted first-pass perfusion MR imaging. Radiology. 2000 Aug;216(2):545-53. PMID: 10924584
  51. Van Goethem M, Biltjes IG, De Schepper AM. Indications for MR mammography. A Belgian study. JBR-BTR. 2000 Jun;83(3):126-9. PMID: 11025925
  52. Kaida H, Ishibashi M, Fuji T, et al. Improved breast cancer detection of prone breast fluorodeoxyglucose-PET in 118 patients. Nucl Med Commun. 2008 Oct;29(10):885-93. PMID: 18769306
  53. Buchmann I, Riedmuller K, Hoffner S, et al. Comparison of 99mtechnetium-pertechnetate and 123iodide SPECT with FDG-PET in patients suspicious for breast cancer. Cancer Biother Radiopharm. 2007 Dec;22(6):779-89. PMID: 18158769
  54. Schirrmeister H, Kuhn T, Guhlmann A, et al. Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures. Eur J Nucl Med. 2001 Mar;28(3):351-8. PMID: 11315604
  55. Yutani K, Shiba E, Kusuoka H, et al. Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis. J Comput Assist Tomogr. 2000 Mar-Apr;24(2):274-80. PMID: 10752892
  56. Mathieu I, Mazy S, Willemart B, et al. Inconclusive triple diagnosis in breast cancer imaging: is there a place for scintimammography? J Nucl Med. 2005 Oct;46(10):1574-81. PMID: 16204705
  57. Habib S, Maseeh-uz-Zaman, Hameed A, et al. Diagnostic accuracy of Tc-99m-MIBI for breast carcinoma in correlation with mammography and sonography. J Coll Physicians Surg Pak. 2009 Oct;19(10):622-6. PMID: 19811712
  58. Kim IJ, Kim SJ, Kim YK. Comparison of double phase Tc-99m MIBI and Tc-99m tetrofosmin scintimammography for characterization of breast lesions: Visual and quantitative analyses. Neoplasma. 2008;55(6):526-31. PMID: 18999882
  59. Kim SJ, Bae YT, Lee JS, et al. Diagnostic performances of double-phase tc-99m MIBI scintimammography in patients with indeterminate ultrasound findings: visual and quantitative analyses. Ann Nucl Med. 2007 Jun;21(3):145-50. PMID: 17561585
  60. Pinero A, Galindo PJ, Illana J, et al. Diagnostic efficiency of sestamibi gammagraphy and Doppler sonography in the preoperative assessment of breast lesions. Clin Transl Oncol. 2006 Feb;8(2):103-7. PMID: 16632424
  61. Grosso M, Chiacchio S, Bianchi F, et al. Comparison between 99mTc-sestamibi scintimammography and X-ray mammography in the characterization of clusters of microcalcifications: a prospective long-term study. Anticancer Res. 2009 Oct;29(10):4251-7. PMID: 19846982
  62. Wang F, Wang Z, Wu J, et al. The role of technetium-99m-labeled octreotide acetate scintigraphy in suspected breast cancer and correlates with expression of SSTR. Nucl Med Biol. 2008 Aug;35(6):665-71. PMID: 18678351
  63. Gommans GM, van der Zant FM, van Dongen A, et al. (99M)Technetium-sestamibi scintimammography in non-palpable breast lesions found on screening X-ray mammography. Eur J Surg Oncol. 2007 Feb;33(1):23-7. PMID: 17126524
  64. Schillaci O, Danieli R, Filippi L, et al. Scintimammography with a hybrid SPECT/CT imaging system. Anticancer Res. 2007 Jan;27(1 B):557-62. PMID: 17348441
  65. Gokalp G, Topal U, Kizilkaya E. Power Doppler sonography: anything to add to BI-RADS US in solid breast masses? Eur J Radiol. 2009 Apr;70(1):77-85. PMID: 18243623
  66. Liu H, Jiang YX, Liu JB, et al. Evaluation of breast lesions with contrast-enhanced ultrasound using the microvascular imaging technique: initial observations. Breast. 2008 Oct;17(5):532-9. PMID: 18534851
  67. Vade A, Lafita VS, Ward KA, et al. Role of breast sonography in imaging of adolescents with palpable solid breast masses. AJR Am J Roentgenol. 2008 Sep;191(3):659-63. PMID: 18716091
  68. Cha JH, Moon WK, Cho N, et al. Characterization of benign and malignant solid breast masses: comparison of conventional US and tissue harmonic imaging. Radiology. 2007 Jan;242(1):63-9. PMID: 17090709
  69. Chala L, Endo E, Kim S, et al. Gray-scale sonography of solid breast masses: diagnosis of probably benign masses and reduction of the number of biopsies. J Clin Ultrasound. 2007 Jan;35(1):9-19. PMID: 17149763
  70. Zhi H, Ou B, Luo BM, et al. Comparison of ultrasound elastography, mammography, and sonography in the diagnosis of solid breast lesions. J Ultrasound Med. 2007 Jun;26(6):807-15. PMID: 17526612
  71. Cho N, Moon WK, Cha JH, et al. Differentiating benign from malignant solid breast masses: comparison of two-dimensional and three-dimensional US. Radiology. 2006 Jul;240(1):26-32. PMID: 16684920
  72. Forsberg F, Goldberg BB, Merritt CR, et al. Diagnosing breast lesions with contrast-enhanced 3-dimensional power Doppler imaging. J Ultrasound Med. 2004 Feb;23(2):173-82. PMID: 14992354
  73. Meyberg-Solomayer GC, Kraemer B, Bergmann A, et al. Does 3-D sonography bring any advantage to noninvasive breast diagnostics? Ultrasound Med Biol. 2004 May;30(5):583-9. PMID: 15183222
  74. Chen DR, Jeng LB, Kao A, et al. Comparing thallium-201 spect mammoscintigraphy and ultrasonography to detect breast cancer in mammographical dense breasts. Neoplasma. 2003;50(3):222-6. PMID: 12937857
  75. Kook SH, Kwag HJ. Value of contrast-enhanced power Doppler sonography using a microbubble echo-enhancing agent in evaluation of small breast lesions. J Clin Ultrasound. 2003 Jun;31(5):227-38. PMID: 12767017
  76. Marini C, Traino C, Cilotti A, et al. Differentiation of benign and malignant breast microcalcifications: mammography versus mammography-sonography combination. Radiol Med. 2003 Jan-Feb;105(1-2):17-26. PMID: 12700541
  77. Reinikainen H, Rissanen T, Paivansalo M, et al. B-mode, power Doppler and contrast-enhanced power Doppler ultrasonography in the diagnosis of breast tumors. Acta Radiol. 2001 Jan;42(1):106-13. PMID: 11167342
  78. Blohmer JU, Oellinger H, Schmidt C, et al. Comparison of various imaging methods with particular evaluation of color Doppler sonography for planning surgery for breast tumors. Arch Gynecol Obstet. 1999;262(3-4):159-71. PMID: 10326635
  79. Chao TC, Lo YF, Chen SC, et al. Prospective sonographic study of 3093 breast tumors. J Ultrasound Med. 1999 May;18(5):363-70. PMID: 10327015
  80. Wilkens TH, Burke BJ, Cancelada DA, et al. Evaluation of palpable breast masses with color Doppler sonography and gray scale imaging. J Ultrasound Med. 1998 Feb;17(2):109-15. PMID: 9527570
  81. Stavros AT, Thickman D, Rapp CL, et al. Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. Radiology. 1995 Jul;196(1):123-34. PMID: 7784555
  82. Ciatto S, Rosselli del Turco M, Catarzi S, et al. The contribution of ultrasonography to the differential diagnosis of breast cancer. Neoplasma. 1994;41(6):341-5. PMID: 7870218
  83. Perre CI, Koot VC, de Hooge P, et al. The value of ultrasound in the evaluation of palpable breast tumours: a prospective study of 400 cases. Eur J Surg Oncol. 1994 Dec;20(6):637-40. PMID: 7995413
  84. Caruso G, Ienzi R, Cirino A, et al. Breast lesion characterization with contrast-enhanced US. Work in progress. Radiol Med. 2002 Nov-Dec;104(5-6):443-50. PMID: 12589266
  85. Koukouraki S, Koukourakis MI, Vagios E, et al. The role of 99mTc-sestamibi scintimammography and colour Doppler ultrasonography in the evaluation of breast lesions. Nucl Med Commun. 2001 Nov;22(11):1243-8. PMID: 11606891
  86. Schroeder RJ, Maeurer J, Vogl TJ, et al. D galactose-based signal-enhanced color Doppler sonography of breast tumors and tumorlike lesions. Invest Radiol. 1999 Feb;34(2):109-15. PMID: 9951790
  87. Buadu LD, Murakami J, Murayama S, et al. Colour Doppler sonography of breast masses: a multiparameter analysis. Clin Radiol. 1997;52:917-23. PMID: 9413965
  88. Zdemir A, Kilic K, Ozdemir H, et al. Contrast-enhanced power Doppler sonography in breast lesions: effect on differential diagnosis after mammography and gray scale sonography. J Ultrasound Med. 2004 Feb;23(2):183-95; quiz 196-7. PMID: 14992355
  89. Milz P, Lienemann A, Kessler M, et al. Evaluation of breast lesions by power Doppler sonography. Eur Radiol. 2001;11(4):547-54. PMID: 11354745
  90. Moon WK, Im JG, Noh DY, et al. Nonpalpable breast lesions: evaluation with power Doppler US and a microbubble contrast agent-initial experience. Radiology. 2000 Oct;217(1):240-6. PMID: 11012451
  91. Albrecht T, Patel N, Cosgrove DO, et al. Enhancement of power Doppler signals from breast lesions with the ultrasound contrast agent EchoGen emulsion: subjective and quantitative assessment. Acad Radiol. 1998 Apr;5 Suppl 1:S195-8; discussion S199. PMID: 9561080
  92. Guidance chapter. In: Breast Imaging Reporting and Data System Atlas (BI-RADS Atlas). BI-RADS - Mammography. 4th ed. Reston (VA): American College of Radiology (ACR); 2003. p. 253-60. www.acr.org/SecondaryMainMenuCategories/quality_safety/ BIRADSAtlas/BIRADSAtlasexcerptedtext/
    BIRADSMammographyFourthEdition/ FollowUpandOutcomeMonitoringDoc4.aspx
     Exit Disclaimer.

Full Report

This executive summary is part of the following document: Bruening W, Uhl S, Fontanarosa J, Reston J, Treadwell J, Schoelles K. Noninvasive Diagnostic Tests for Breast Abnormalities: Update of a 2006 Review. Comparative Effectiveness Review No. 47. (Prepared by the ECRI Institute Evidence-based Practice Center under Contract No. 290-02-0019.) AHRQ Publication No. 12-EHC014-EF. Rockville, MD: Agency for Healthcare Research and Quality; February 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

For More Copies

For more copies of Noninvasive Diagnostic Tests for Breast Abnormalities: Update of a 2006 Review: Comparative Effectiveness Review Executive Summary No. 47 (AHRQ Pub. No. 12-EHC014-1), please call the AHRQ Clearinghouse at 1-800-358-9295 or email ahrqpubs@ahrq.gov.

Return to Top of Page