Probably benign lesions at screening breast US in a population with elevated risk: Prevalence and rate of malignancy in the ACRIN 6666 trial

Purpose: To prospectively validate predefined breast ultrasonographic (US) Breast Imaging Reporting and Data System (BI-RADS) category 3 criteria in a multicenter setting in an elevated-risk population. Materials and Methods: The American College of Radiology Imaging Network 6666 database was reviewed for prospectively defined BI-RADS category 3 lesions. Patient characteristics, lesion US features at initial detection, and work-up recommendations were analyzed with descriptive statistics. Exact 95% confidence intervals (CIs) were given, where appropriate. Lesion reference standard was biopsy or a minimum of 1-year follow-up. In addition, malignancy rate for lesions that had at least 2 years of follow-up data or that had biopsy data was calculated. Results: Of 2662 participants, 519 (19.5%) had 745 BI-RADS category 3 lesions (25.5% of 2916 US lesions other than simple cysts), with a median size of 7 mm (range, 2-135 mm). The number of new BI-RADS category 3 lesions decreased with year 2-3 screening, but the percentage of new BI-RADS category 3 lesions was stable at 26.4% (506 of 1920 lesions), 23.6% (142 of 601 lesions), and 24.6% (97 of 395 lesions), respectively. Of 745 BI-RADS category 3 lesions, 124 (16.6%) were ultimately sampled for biopsy. Six malignancies (0.8% of BI-RADS category 3 lesions; 95% confidence interval [CI]: 0.3%, 1.7%) occurred in five (1.0%) of 519 participants: Five malignancies were invasive (median size, 10 mm; size range, 2-18 mm), and one was node positive. When the analysis is limited to lesions with at least 2-year follow-up or biopsy, the malignancy rate among BI-RADS category 3 lesions is 0.9% (95% CI: 0.3%, 2.0%). Three malignant BI-RADS category 3 lesions were sampled for biopsy because of a suspicious change at follow-up (two N0 lesions, one each at 6-and 12-month follow-up; one N1 lesion at 24-month follow-up), one was sampled for biopsy because of an upgrade after additional mammography (NX), one was found at mastectomy for another cancer (N0), and one was found at prophylactic contralateral mastectomy in the same patient (NX). Conclusion: As BI-RADS category 3 lesions have a low malignancy rate (0.8%; 95% CI: 0.3%, 1.7%) and only 0.1% of the cancers had suspicious changes at 6-month follow-up and only one (17%; 95% CI: 0.4%, 64%) of six malignancies were node positive at detection (24-month follow-up), a recommendation of 1-year diagnostic follow-up may be appropriate for BI-RADS category 3 lesions detected at screening US.