Screening ultrasound (US) may depict small, node-negative breast cancers not seen on mammography (M).
To compare the diagnostic yield (proportion of women with a positive screen test and positive reference standard) and performance of screening with US+M compared to M alone in women at elevated risk of breast cancer.
Design, Setting, and Participants
From April 2004 to February 2006, 2809 women at elevated risk for breast cancer, with at least heterogeneously dense breast tissue in at least one quadrant, were recruited from 21 IRB-approved sites to undergo mammography (M) and physician-performed ultrasound (US) exams in randomized order by a radiologist masked to the results of the other exam. Reference standard was defined as a combination of pathology and 12 month follow-up, and was available for 2637 out of the 2725 eligible participants.
Main Outcome Measure
Diagnostic yield, sensitivity, specificity, and AUC of combined M+US compared to M alone; PPV of biopsy recommendations for M+US compared to M alone.
Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both US and M, 12 on US alone, 12 on M alone, and 8 participants (9 breasts) on neither (interval cancers). The diagnostic yield for M was 7.6 per 1000 women screened (20/2637) and increased to 11.8 per 1000 (31/2637) for combined US+M; the supplemental yield was 4.2 per 1000 women screened (95% CI 1.1 to 7.2 per 1000; p = 0.003 that the supplemental yield is zero). The diagnostic accuracy (AUC) for M was 0.78 (95% CI 0.67 to 0.87) and increased to 0.91 (95% CI 0.84 to 0.96) for US+M (p = 0.003 that difference is zero). Of 12 supplemental cancers seen only by US, 11 (92%) were invasive with median size 10 mm (range 5 to 40 mm; mean 12.6, SE 3.0) and 8/9 (89%) reported had negative nodes. PPV of biopsy recommendation after full diagnostic workup (PPV2) was 84/276 for M (22.6%, 95% CI 14.2 to 33%), 21/235 for US (8.9%, 95% CI 5.6 to 13.3%), and 31/276 for combined US+M (11.2%, 95% CI 7.8 to 15.6%).
Adding a single screening US to M will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but will also substantially increase the number of false positives. Evaluation of the role of annual screening US is ongoing in this patient population. [Clinicaltrials.gov registry # NCT00072501]