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

Wendie A. Berg, 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

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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 10mm (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.

Original languageEnglish (US)
Pages (from-to)2151-2163
Number of pages13
JournalJAMA - Journal of the American Medical Association
Volume299
Issue number18
DOIs
StatePublished - May 14 2008

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Mammary Ultrasonography
Mammography
Breast Neoplasms
Confidence Intervals
Breast
Biopsy
Neoplasms
ROC Curve
Outcome Assessment (Health Care)
Pathology
Physicians
Sensitivity and Specificity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Berg, W. A., Blume, J. D., Cormack, J. B., Mendelson, E. B., Lehrer, D., Böhm-Vélez, M., ... Boparai, K. (2008). Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA - Journal of the American Medical Association, 299(18), 2151-2163. https://doi.org/10.1001/jama.299.18.2151

Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. / Berg, Wendie A.; Blume, Jeffrey D.; Cormack, Jean B.; Mendelson, Ellen B.; Lehrer, Daniel; Böhm-Vélez, Marcela; Pisano, Etta D.; Jong, Roberta A.; Evans, W. Phil; Morton, Marilyn J.; Mahoney, Mary C.; Larsen, Linda Hovanessian; Barr, Richard G.; Farria, Dione M.; Marques, Helga S.; Boparai, Karan.

In: JAMA - Journal of the American Medical Association, Vol. 299, No. 18, 14.05.2008, p. 2151-2163.

Research output: Contribution to journalArticle

Berg, WA, Blume, JD, Cormack, JB, Mendelson, EB, Lehrer, D, Böhm-Vélez, M, Pisano, ED, Jong, RA, Evans, WP, Morton, MJ, Mahoney, MC, Larsen, LH, Barr, RG, Farria, DM, Marques, HS & Boparai, K 2008, 'Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer', JAMA - Journal of the American Medical Association, vol. 299, no. 18, pp. 2151-2163. https://doi.org/10.1001/jama.299.18.2151
Berg, Wendie A. ; Blume, Jeffrey D. ; Cormack, Jean B. ; Mendelson, Ellen B. ; Lehrer, Daniel ; Böhm-Vélez, Marcela ; Pisano, Etta D. ; Jong, Roberta A. ; Evans, W. Phil ; Morton, Marilyn J. ; Mahoney, Mary C. ; Larsen, Linda Hovanessian ; Barr, Richard G. ; Farria, Dione M. ; Marques, Helga S. ; Boparai, Karan. / Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. In: JAMA - Journal of the American Medical Association. 2008 ; Vol. 299, No. 18. pp. 2151-2163.
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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 10mm (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.",
author = "Berg, {Wendie A.} and Blume, {Jeffrey D.} and Cormack, {Jean B.} and Mendelson, {Ellen B.} and Daniel Lehrer and Marcela B{\"o}hm-V{\'e}lez and Pisano, {Etta D.} and Jong, {Roberta A.} and Evans, {W. Phil} and Morton, {Marilyn J.} and Mahoney, {Mary C.} and Larsen, {Linda Hovanessian} and Barr, {Richard G.} and Farria, {Dione M.} and Marques, {Helga S.} and Karan Boparai",
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TY - JOUR

T1 - Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer

AU - Berg, Wendie A.

AU - Blume, Jeffrey D.

AU - Cormack, Jean B.

AU - Mendelson, Ellen B.

AU - Lehrer, Daniel

AU - Böhm-Vélez, Marcela

AU - Pisano, Etta D.

AU - Jong, Roberta A.

AU - Evans, W. Phil

AU - Morton, Marilyn J.

AU - Mahoney, Mary C.

AU - Larsen, Linda Hovanessian

AU - Barr, Richard G.

AU - Farria, Dione M.

AU - Marques, Helga S.

AU - Boparai, Karan

PY - 2008/5/14

Y1 - 2008/5/14

N2 - 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 10mm (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.

AB - 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 10mm (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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