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Randomized Controlled Trial
. 2008 May 14;299(18):2151-63.
doi: 10.1001/jama.299.18.2151.

Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer

Wendie A Berg  1 , Jeffrey D Blume, Jean B Cormack, Ellen B Mendelson, Daniel Lehrer, Marcela Böhm-Vélez, Etta D Pisano, Roberta A Jong, W Phil Evans, Marilyn J Morton, Mary C Mahoney, Linda Hovanessian Larsen, Richard G Barr, Dione M Farria, Helga S Marques, Karan Boparai; ACRIN 6666 Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer

Wendie A Berg et al. JAMA. .

Erratum in

  • JAMA. 2010 Apr 21;303(15):1482

Abstract

Context: Screening ultrasound may depict small, node-negative breast cancers not seen on mammography.

Objective: To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer.

Design, setting, and participants: From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants.

Main outcome measures: Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone.

Results: Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%).

Conclusions: Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives.

Trial registration: clinicaltrials.gov Identifier: NCT00072501.

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Figures

Fig. 1
Fig. 1
Flowchart of protocol.
Fig. 2
Fig. 2
ROC curves based on expanded BI-RADS assessments for mammography alone (solid line), combined mammography and ultrasound (dashed line), and ultrasound alone (dashed and dotted line). Table 2 presents summary statistics for these curves. The ultrasound ROC is included for completeness; the study was not designed to permit direct comparison to ultrasound alone.
See this image and copyright information in PMC

Comment in

References

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