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Robinson KA, Maimone S, Gococo-Benore DA, Li Z, Advani PP, Chumsri S. Incidence of Axillary Adenopathy in Breast Imaging After COVID-19 Vaccination. JAMA Oncol. 2021;7(9):1395–1397. doi:10.1001/jamaoncol.2021.3127
Vaccine-induced adenopathy after COVID-19 vaccination in breast imaging has received significant media attention, with evolving literary correspondence on management. Patients’ self-report of axillary swelling following COVID-19 vaccination was reported as high as 16%.1 The National Comprehensive Cancer Network and Society of Breast Imaging recommended to consider scheduling screening breast imaging 4 to 6 weeks after the second COVID-19 vaccination dose when possible.2 However, the actual incidence, timing, and characteristics of mammographic axillary adenopathy following COVID-19 vaccination remain uncertain.
Retrospective analysis was carried out assessing patients who received at least 1 injection of COVID-19 vaccine fewer than 90 days prior to either screening or diagnostic mammography at the Jacoby Center for Breast Health, Mayo Clinic, Florida, between January 15 and March 22, 2021. Information regarding COVID-19 vaccination and symptomatic adenopathy was inquired by technicians performing mammography and documented in the electronic medical record. Axillary adenopathy was assessed by interpreting radiologists and all adenopathy cases were re-reviewed. Wilcoxon rank-sum test and Fisher exact test were used to compare continuous and categorical variables, respectively. Multivariable logistic regression model was used to evaluate the association between days from vaccine and adenopathy. Receiver operating curve (ROC) analysis was used to assess potential cutoff days after vaccine and adenopathy. The analysis was done using R version 3.6.2. This study and waiver of informed consent were approved by Mayo Clinic Institutional Review Board.
Of 750 women total, 23 (3%) patients had axillary adenopathy on mammography and only 2 patients were symptomatic (Table). As summarized in the Table, presence of symptoms was associated with abnormal imaging (40% vs 60%, P = .01) but not age (median [range] 64 [35-83] vs 67 [31-94]; P = .29) and type of vaccine (P = .70). Most patients with adenopathy had their second vaccination prior to breast imaging (18 out of 23 patients). However, there was no significant difference between the incidence of adenopathy after the first or second vaccination (P = .34).
The median time after vaccine in patients with adenopathy was significantly shorter at 10 days compared with 18 days in patients without adenopathy (median [range] 10 [1-28] vs 18 [1-85] days; P < .001). Adenopathy rates decreased as days from vaccine increased with 15 of 283 (5.3%) for 1 to 14 days, 8 of 272 (2.9%) for 15 to 28 days, and 0 of 195 (0%) for more than 28 days (P = .01). Using ROC analysis to identify the potential cutoff value of days after vaccination, the area under the ROC curve was 0.72 (95% CI, 0.63-0.81) with the potential cutoff of 22.5 days.
The spectrum of mammography findings ranged from a single enlarged lymph node, to multiple enlarged lymph nodes, to adenopathy with soft tissue stranding. Additional imaging with ultrasonography was requested for 21 patients. At the time of this article, 17 ultrasonography examinations had been performed. Ultrasonography findings ranged from mildly prominent nodes with a preserved fatty hilum to rounded nodes demonstrating apparent loss of a fatty hilum. Follow-up imaging recommendations included no follow-up (n = 2), repeated ultrasonography with or without mammogram in 3 months (n = 14), and biopsy (n = 1). Biopsy was recommended for a patient with an ipsilateral breast cancer. Biopsy findings for this patient were negative for malignancy, and the adenopathy was presumably vaccine induced.
While the incidence of COVID-19 vaccine-induced adenopathy in our study appeared to be low at 3% compared with 16% of self-reported axillary swelling in previous COVID-19 vaccine trials, this incidence is still higher than axillary adenopathy in otherwise normal mammography, which was reported as 0.02% to 0.04%.3 Therefore, routine inquiring about recent history of COVID-19 vaccination is warranted. The incidence of adenopathy decreased over time with no adenopathy seen in patients who received the vaccine more than 28 days previously, which supports the recommendations from Society of Breast Imaging. In addition, patients with symptomatic adenopathy are more likely to have adenopathy (odds ratio, 28.97; 95% CI, 3.23-226.09; P = .01). However, the present study has limitations, particularly with its small sample size and being a single center study. As COVID-19 vaccination is rolling out around the world, this study offers timing considerations and possible findings for breast imaging following vaccination. Further studies are needed to guide future recommendations for following up with patients with adenopathy after vaccination and evaluating findings with other imaging modalities.
Accepted for Publication: May 25, 2021.
Published Online: July 22, 2021. doi:10.1001/jamaoncol.2021.3127
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Robinson KA et al. JAMA Oncology.
Corresponding Author: Saranya Chumsri, MD, Division of Hematology and Medical Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224 (firstname.lastname@example.org).
Author Contributions: Dr Chumsri had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Robinson, Maimone, Advani, Chumsri.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Robinson, Maimone, Advani, Chumsri.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Maimone, Li, Advani, Chumsri.
Obtained funding: Chumsri.
Administrative, technical, or material support: Chumsri.
Supervision: Maimone, Chumsri.
Conflict of Interest Disclosures: Dr Advani reported grants from Genentech during the conduct of the study. Dr Chumsri reported grants from Pfizer during the conduct of the study; grants from Merck & Co, the Department of Defense, and the Breast Cancer Research Foundaiton; and personal fees from Novartis, Immunomedics, Puma Biotechnology, BioTheranostics, AstraZeneca, Eisai, Athenex, and Daiichi Sankyo outside the submitted work. No other disclosures were reported.
Funding/Support: Research reported in this publication was supported by Mayo Clinic.
Role of the Funder/Sponsor: The Mayo Clinic had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.