The risk of breakthrough SARS-CoV-2 infection in vaccinated cancer patients varies by cancer type, according to a large database study published in JAMA Oncology.

Researchers found the highest rate of breakthrough infections in patients with pancreatic cancer (24.7%), liver cancer (22.8%), lung cancer (20.4%), and colorectal cancer (17.5%).

Rates of breakthrough infection were lower for thyroid cancer (10.3%), endometrial cancer (11.9%), breast cancer (11.9%), and hematologic cancers (14.9%). Still, these rates were all significantly higher than the breakthrough infection rate in the non-cancer population (4.9%; P <.001 for all).

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This study was conducted using the TriNetX Analytics network platform, which contains data on 90 million unique inpatients and outpatients from 66 health care organizations.

Researchers examined the electronic health records of 636,465 vaccinated patients from December 2020 through November 2021. The cohort included 45,253 patients with the 12 most common cancers in the United States (bladder, breast, colorectal, endometrial, hematologic, kidney, liver, lung, pancreatic, prostate, skin, and thyroid).

All patients had proof of full vaccination — 2 doses of the Moderna or Pfizer-BioNTech COVID-19 vaccines or a single dose of the Janssen/Johnson & Johnson vaccine. Individuals with a prior history of SARS-CoV-2 infection were excluded.

Overall, the risk of breakthrough SARS-CoV-2 infections was significantly higher in patients with cancer than in patients without cancer (hazard ratio [HR], 1.24; 95% CI, 1.19-1.29).

The risk of breakthrough infections was highest for liver cancer and lowest for thyroid cancer. The risk by cancer type was:

  • Liver cancer — HR, 1.78 (95% CI, 1.38-2.29)
  • Lung cancer — HR, 1.73 (95% CI, 1.50-1.99)
  • Pancreatic cancer — HR, 1.64 (95% CI, 1.24-2.18)
  • Colorectal cancer — HR, 1.53 (95% CI, 1.32-1.77)
  • Bladder cancer — HR, 1.43 (95% CI, 1.21-1.69)
  • Kidney cancer — HR, 1.33 (95% CI, 1.12-1.58)
  • Endometrial cancer — HR, 1.32 (95% CI, 1.05-1.66)
  • Hematologic cancer — HR, 1.28 (95% CI, 1.16-1.42)
  • Prostate cancer — HR, 1.19 (95% CI, 1.10-1.29)
  • Skin cancer — HR, 1.17 (95% CI, 0.99-1.38)
  • Breast cancer — HR, 1.16 (95% CI, 1.07-1.25)
  • Thyroid cancer — HR, 1.07 (95% CI, 0.88-1.30).

Having a medical encounter for cancer within the past 12 months was associated with a higher risk of breakthrough infection (HR, 1.24; 95% CI, 1.18-1.31).

Among patients with cancer, the overall rate of hospitalization was higher for patients with a breakthrough infection than for those without a breakthrough infection— 31.6% and 3.9%, respectively (HR, 13.48; 95% CI, 11.42-15.91). The mortality rate was 6.7% and 1.3%, respectively (HR, 6.76; 95% CI, 4.97-9.20).

The researchers noted that this study is limited by its observational and retrospective nature. However, the results suggest a need for additional measures to protect vaccinated cancer patients from breakthrough infections.

“With the emergence of SARS-CoV-2 virus variants and the waning immunity of vaccines, the findings raise the consideration for the development and implementation of enhanced mitigation strategies in vaccinated patients with specific cancers, especially those undergoing active cancer care,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wang W, Kaelber DC, Xu R, Berger NA. Breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with cancer in the US between December 2020 and November 2021. JAMA Oncol. Published online April 8, 2022. doi:10.1001/jamaoncol.2022.1096