Prevalence of Acute and Delayed Contrast Reactions With Multiple Exposures to Contrast-Enhanced Mammography—Experience From the TOCEM Trial

Objective To detail acute and delayed contrast reactions associated with contrast-enhanced mammography (CEM) in a prospective screening trial. Methods In an institutional review board–approved protocol from October 2019 through July 2024, women with personal history of breast cancer received up to 3 rounds of annual supplemental screening CEM. Intravenous iopamidol (370 mg/mL) was administered via automated injector. Adverse events within 1 week of contrast administration were recorded. Results A total of 1651 women (mean age at entry: 63.2 years) received 3873 contrast injections (1651, 1326, and 896 in years 1, 2, and 3, respectively). Among 3873 injections, we observed 38 (0.98%) contrast reactions in 35 unique participants, including 25/3873 (0.65%) allergic-like reactions (15/1651 [0.91%] in year 1, 7/1326 [0.53%] in year 2, and 3/896 [0.33%] in year 3), 9/3873 (0.23%) physiologic reactions, and 4/3873 (0.10%) other reactions. Of 25 allergic-like reactions, 20 (80%) were cutaneous (hives/rash). One participant had bronchospasm, 1 had scratchy throat, 1 had shortness of breath, 1 sneezed repeatedly, and 1 had watery eyes. Five allergic-like reactions were delayed, including hives in 4 (2 at 1 day, 1 at 2-3 days, and one 7 days later) and watery eyes in 1; 2 physiologic reactions were delayed. Two of 25 reactions were immediate, and imaging was not completed; medication was given to 15/25 (60%). Allergic-like reactions occurred in 14/3328 (0.42%) examinations in women with prior uneventful iodinated contrast exposure, 10/510 (1.96%) among those naïve to contrast (P <.001), and 1 woman with recurrent but initially unreported reaction in year 1. No allergic-like reactions were observed in 34 examinations (19 women) premedicated for prior allergic contrast reaction. Conclusion We observed a low rate and usually mild severity of adverse reactions to iodinated contrast in CEM with trained staff.