COVID-19 has had devastating effects on the world population. Vaccination has had a significant effect on reducing mortality and mortality from SAR-CoV2. The campaign to vaccinate the world against this deadly disease has been historic, with over 1 billion doses administered in the U.S. and Europe. With the widespread administration of the COVID-19 vaccines, reports have surfaced of the development of regional lymphadenopathy. This may be an especially concerning finding in patients with BC.

A recent literature review examined the available evidence on vaccine-related lymphadenopathy and its clinical implications on BC diagnosis and management. Databases included PubMed, Ovid Medline, Scopus, CINHAL, Springer Nature, Science Direct, Academic Search Premier, the Directory of Open Access Journals, Google Scholar, and ResearchGate. They were searched from January through May 9, 2021 for association of the Pfizer, Moderna, Janssen, and AstraZeneca COVID-19 vaccines and the development of lymphadenopathy.

Studies were included only if there was a diagnosis of lymphadenopathy present under the following situations: palpable adenopathy in a patient with a symptomatic presentation, upon a breast screening examination, as an incidental finding during a screening exam, or while staging BC or during follow-up exams. Case studies and case series with fewer than 50 patients were excluded from analysis.

A collection of case studies of vaccine-related regional lymphadenopathy was also compiled for diagnostic and therapeutic purposes.

In total, 15 studies met inclusion criteria. Of the 2,057 patients included in these trials, 737 had vaccine-related lymphadenopathy. Over 50% of the clinical trials (8/15) involved the Pfizer mRNA COVID-19 vaccine. Two of the 15 trials involved Moderna's vaccine, three trials involved a combination of Pfizer and Moderna, and two of the trials did not indicate which vaccine was administered.

In total, 1,980 study subjects had received the Pfizer vaccine. Postvaccination lymphadenopathy was observed in 14.5% after a single dose of the Pfizer vaccine. Rates of lymphadenopathy increased following the second Pfizer vaccine with rates reported of over 50%. Factors associated with a lower risk of developing lymphadenopathy included receiving only the first dose of the vaccine, patients aged 64 years or older, and being in an immunocompromised status. Lymphadenopathy most often occurred in patients aged younger than age 64 years, immunocompetent patients, and those who were fully vaccinated (not considering booster shots).

Lymphadenopathy was further classified as nonpalpable or palpable. Almost all cases (98.3%) of nonpalpable lymphadenopathy were located in the axilla, and 0.3% of cases had enlarged supraclavicular fossa lymph nodes.  For palpable lymphadenopathy, the reverse was true, with 86.5% of subject participants developing enlargement of their supraclavicular fossa nodes; only 10.8% had axilla adenopathy, and 2.7% had a combination of both nodal enlargements.

In most cases, especially for palpable lymphadenopathy, resolution of lymphedema occurred in 7 to 8 days. However, in almost 30% of cases, PET/CT scans showed that lymphadenopathy persisted for 3 weeks, and in some cases, beyond 6 weeks. Despite these findings, only about 1% of cases of lymphadenopathy were considered suspicious and resulted in further follow-up testing.
Although not a direct finding of this study, in the Discussion section, the authors report that the Moderna vaccine has been associated with an incidence of 11.6% and 16% for ipsilateral axillary lymphadenopathy following administration of the first and second doses of the mRNA vaccine, respectively.

General advice is available regarding the timing of BC screening. Pharmacists need to be aware of these suggestions since they have taken on the role of primary immunizers. In the U.S., it is generally recommended to perform breast screening exams either before receiving the COVID-19 vaccine or 6 to 10 weeks after the second dose to avoid diagnostic confusion should lymphadenopathy occur. Further, women with a history of BC should receive the COVID-19 vaccine in the contralateral (opposite) arm of the side in which they had BC.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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