Although not mandatory, Singapore offers free COVID-19 vaccination under the National Vaccination Programme for citizens and long-term residents during the pandemic. Globally, Singapore is third country after Qatar and Brunei with the highest proportion of population vaccinated (90.9%) [19, 20]. Nevertheless, a small fraction of our population, including cancer patients, remained hesitant on COVID-19 vaccination primarily due to vaccine safety and efficacy concerns. Under the Singapore healthcare framework, individuals with cancer on active treatment or those in remission are given recommended for COVID-19 vaccine if deemed eligible by their primary physician. Patients on active treatment are considered to be at least moderately immunocompromised and are further encouraged to receive a third dose of vaccine 2 months after their second dose [21]. Conceivably, individuals with inherited genetic disorders associated with impaired immune function will also stand to benefit from these vaccination strategies.

In our evaluated cohort of BRCA1/2 germline PV/LPV carriers, a greater proportion of cancer patients were female (95%) compared to non-cancer patients (64%), and cancer patients were older than non-cancer patients. This is in agreement with literature, where male with BRCA1/2 PV/LPV are often silent carriers [22]. Consistent with the Singapore general population (data up to December 2021) [19, 21], our cohort of 189 germline PV/LPV carriers in BRCA1/2 revealed a 90% COVID-19 vaccination uptake rate, predominantly for Pfizer-BioNTech/Comirnaty or Moderna/Spikevax mRNA vaccines and had completed the two-dose primary vaccination schedule at the time of our survey.

At least half of the responders developed post-vaccination side effects, most frequently myalgia followed by fever, which is consistent with side effects typically observed following flu vaccinations. This profile is similar to that reported in other COVID-19 vaccination studies on cancer patient cohorts [15, 16]. None of the demographic variables tested predicted for the occurrence of side effects. There were no major adverse events, such as anaphylaxis or hospitalizations, reported by our study responders. The nature of side effects post-vaccination from our survey were similar to the vaccine studies reported on the Centre for Disease Control and Prevention (CDC) website, with the most common being fatigue, headache and myalgia regardless of age [23]. Although participants were not asked grade of the side effects, the reporting of events in a categorical manner allowed us to compare the observations reported by CDC. The frequency of side effects on CDC was in the range of 70.6 to 82.8% depending on age groups for the Pfizer-BioNTech COVID-19 vaccine and was approximately 55% in our cohort with a median age of 50 years old. In the age group between 18 and 55 years of age the percentage of individuals reported to have local reactions such as redness and swelling was between 4.5 to 6.3%, comparable with our participants with rashes at 6.5%. Reported “fever and chills” in the CDC groups was between 3.7 to 35.1%, while 40.2% of our participants experienced fever. Higher number of headache was reported at 41.9% in the CDC group while 16.3% of our participants had headache post vaccination. Our participants reported lower percentage of fatigue at 11.2% while CDC was between 47.4 to 59.4%. Our results were also similar to a local study evaluating the side effects after COVID-19 vaccination among 1704 healthcare workers (HCW) in Singapore. The HCW responded to an online survey after receiving two doses of Pfizer BioNTech/Comirnaty, most documented side effects of fever (9.3–44.7%), headache (18.8–41.7%), myalgia (30.1–51.9%) and none reported severe reactions, such as anaphylaxis [24].

A clinically relevant side effect of COVID-19 vaccination is the enlargement of axillary lymph nodes on the ipsilateral arm of vaccination site. In a literature review of 15 studies, the reported incidence of regional lymphadenopathy was 14.5–53.0% and persisted for more than 6 weeks in 29.0% of recipients [25]. Most lymphadenopathies (32%) in the study were detected on imaging whereas only 1.8% were self-reported. Our cohort had 3 (1.8%) vaccinated responders with reported lymphadenopathy. As part of regular surveillance for breast cancer, PV/LPV carriers of BRCA1/2 are recommended for annual breast magnetic resonance imaging and breast mammogram as early as age 25 years and hence, it may be prudent for physicians to advise COVID-19 vaccine recipients to defer imaging scans minimally a few weeks post-vaccination to avoid false positives for pathological conditions.

Our study is limited by the small sample size, mostly due to a notable (28.3%) non-responding rate to our phone call survey, and lack of a control cohort without germline PV/LPV in BRCA1/2 for statistical evaluation. As side effects were self-reported by responders, our assessment could be an underestimate due to subjectivity across individuals and the questionnaire used precluded evaluation of any temporal relationship between side effects and vaccine dose. Nevertheless, our observations on the side effects profile were consistent with the general Singapore population and other cancer patient cohorts, defined by predominantly mild and self-limiting effects such as myalgia, fever and headache with no severe side effects.