Probably Benign or Higher Risk? Re-Assessing Management of MRI BI-RADS 3 Lesions in the Contralateral Breast of Women with Diagnosed Unilateral Breast Cancer

<title>Abstract</title> <p>Background &amp; Aims: Women with newly diagnosed unilateral breast cancer frequently undergo preoperative breast MRI, which often reveals “probably benign” (BI-RADS 3) findings in the contralateral breast. Whether these lesions truly meet the universal BI-RADS 3 malignancy threshold (&lt; 2%) in this high-risk setting is uncertain. We aimed to determine the malignancy rate of contralateral MRI BI-RADS 3 lesions and to identify imaging features that refine management. Methods We performed a post-hoc study of the multicenter, prospective ACRIN 6667 cohort. 119 patients with 152 contralateral MRI BI-RADS 3 lesions were included. Lesion morphology and patient factors were recorded. The primary outcome was malignancy rate compared with the 2% benchmark. Results Overall, 13 of 152 contralateral BI-RADS 3 lesions were malignant equaling 8.6% (p &lt; 0.001 vs 2%). Rates were similarly elevated for solitary (8.2%; p &lt; 0.001) and multiple BI-RADS 3 lesions (9.1%; p = 0.006). Small foci and non-mass enhancement carried the highest risks: 12.0% (p &lt; 0.001) and 10.3% (p = 0.002), respectively, whereas mass lesions had a non-significant 2.4% rate (p = 1.0). Malignancy was more frequent in women &lt; 50 years (12.2%; p &lt; 0.001) than ≥ 50 years (4.2%; p = 0.217). Conclusion Contralateral MRI BI-RADS 3 lesions in women with active unilateral breast cancer have malignancy rates far above the traditional “probably benign” threshold, particularly for young women, small foci and non-mass enhancement. Routine short-interval surveillance may be unsafe in this setting; more aggressive, biopsy-oriented evaluation should be strongly considered for these high-risk stratifications.</p>