BACKGROUND. The variable clinical course of subclinical lymphadenopathy detected on breast imaging after COVID-19 vaccination creates management challenges and has led to evolving practice recommendations. OBJECTIVE. The purpose of this study was to assess the duration of axillary lymphadenopathy ipsilateral to COVID-19 vaccination detected by breast imaging and to assess factors associated with the time until resolution. METHODS. This retrospective single-center study included 111 patients (mean age, 52 ± 12 years) with unilateral axillary lymphadenopathy ipsilateral to mRNA COVID-19 vaccine administration performed within the prior 8 weeks that was detected on breast ultrasound performed between January 1, 2021, and October 1, 2021, and who underwent follow-up ultrasound examinations at 4- to 12-week intervals until resolution of the lymphadenopathy. Patient information was extracted from medical records. Cortical thickness of the largest axillary lymph node on ultrasound was retrospectively measured and was considered enlarged when greater than 3 mm. Multivariable linear regression analysis was used to identify independent predictors of time until resolution. RESULTS. The mean cortical thickness at the initial ultrasound examination was 4.7 ± 1.2 mm. The lymphadenopathy resolved a mean of 97 ± 44 days after the initial ultrasound examination, 127 ± 43 days after the first vaccine dose, and 2.4 ± 0.6 follow-up ultrasound examinations. A significant independent predictor of shorter time to resolution was Pfizer-BioNTech (rather than Moderna) vaccination (β = -18.0 [95% CI, -34.3 to -1.7]; p = .03]. Significant independent predictors of longer time to resolution were receipt of the second dose after the initial ultrasound examination (β = 19.2 [95% CI, 3.1-35.2]; p = .02) and greater cortical thickness at the initial ultrasound examination (β = 8.0 [95% CI, 1.5-14.5]; p = .02). Patient age, history of breast cancer, and axillary symptoms were not significantly associated with time to resolution (all p > .05). CONCLUSION. Axillary lymphadenopathy detected with breast ultrasound after COVID-19 mRNA vaccination lasts longer than reported in initial vaccine clinical trials. CLINICAL IMPACT. The prolonged time to resolution supports not delaying screening mammography because of recent COVID-19 vaccination. It also supports the professional society recommendation of a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

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