Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk

Context: Annual ultrasound screening may detect small, node-negative breast cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may reveal additional breast cancers missed by both mammography and ultrasound screening. Objective: To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer. Design, Setting, and Participants: From April 2004-February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of both screenings, 612 of 703womenwhochose to undergo anMRIhad complete data. The reference standard was defined as a combination of pathology (biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes) and 12-month follow-up. Main Outcome Measures: Cancer detection rate (yield), sensitivity, specificity, positive predictive value (PPV3) of biopsies performed and interval cancer rate. Results: A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 ofwhomhad 111 breast cancer events: 33 detected by mammography only, 32 by ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11 were not detected by any imaging screen. Among 4814 incidence screens in the second andthird years combined,75womenwere diagnosed with cancer. Supplemental incidencescreening ultrasound identified 3.7 cancers per 1000 screens (95% CI, 2.1-5.8; P<.001). Sensitivity for mammography plus ultrasound was 0.76 (95% CI, 0.65-0.85); specificity, 0.84(95%CI, 0.83-0.85);andPPV3, 0.16(95%CI, 0.12-0.21). Formammographyalone, sensitivity was 0.52(95%CI, 0.40-0.64); specificity, 0.91(95%CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28-0.49; P<.001 all comparisons). Of the MRI participants, 16 women (2.6%) had breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI, 3.5-25.9; P=.004). Sensitivity for MRI and mammography plus ultrasound was 1.00 (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95% CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI, 0.20- 0.70, P=.004); specificity 0.84 (95% CI, 0.81-0.87; P<.001); and PPV3, 0.18 (95% CI, 0.08 to 0.34; P=.98). The number of screens needed to detect 1 cancer was 127(95%CI, 99-167) for mammography; 234(95%CI, 173-345) for supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative mammography and ultrasound results. Conclusion: The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings. Trial Registration: clinicaltrials.gov Identifier: NCT00072501.