Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer

Abstract

Purpose: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice.

Methods: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR₂₈) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis.

Results: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR₂₈ demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR₂₈ (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls.

Conclusion: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

FIG 1.

Measures of COVID-19 severity across different pandemic phases (prevaccination, Alpha-Delta, and Omicron). Rates of COVID-19 outcomes are calculated with 95% Wilson CIs, as events occurred for each outcome per number of patients observed in each phase, excluding missing data. Cross-groups comparison P value is provided as subheadings. Intergroup comparison P values with prevaccination phase as reference term and events/patients ratio are also provided. Overall missing/excluded events were: 4 CFR₂₈, 5 ICU admission, 63 hospitalization (5 missing/58 pre-existing), 56 oxygen therapy requirement, 53 COVID-19 specific therapy. (A) CFR₂₈: prevaccination (54/388), Alpha-Delta (20/164), and Omicron (3/57). (B) COVID-19 complications: prevaccination (102/392), Alpha-Delta (41/164), and Omicron (4/57). (C) Hospitalization due to COVID-19: prevaccination (204/358), Alpha-Delta (70/143), and Omicron (12/49). (D) COVID-19–specific therapy: prevaccination (215/363), Alpha-Delta (67/152), and Omicron (9/45). (E) Oxygen therapy requirement: prevaccination (147/367), Alpha-Delta (52/149), and Omicron (8/41). (F) ICU admission: prevaccination (29/391), Alpha-Delta (14/161), and Omicron (1/56). CFR₂₈, 28-day case fatality rate; ICU, intensive care unit.

FIG 2.

Measures of COVID-19 severity across different pandemic phases (prevaccination, Alpha-Delta, and Omicron) according to the vaccination status. Partially vaccinated patients were included among unvaccinated patients to increase the sample size of subgroups. Rates of COVID-19 outcomes are calculated with 95% Wilson CIs, as events occurred for each outcome per number of patients observed in each phase, excluding missing data. Events/patients ratio is also provided. Overall missing/excluded events were: 4 CFR₂₈, 3 ICU admission, 57 hospitalization, 48 oxygen therapy requirement, 46 COVID-19 specific therapy. (A) CFR₂₈: prevaccination (54/388), Alpha-Delta unvaccinated (15/113), Omicron unvaccinated (2/8), Alpha-Delta vaccinated (2/26), and Omicron vaccinated (1/46). (B) COVID-19 complications: prevaccination (102/392), Alpha-Delta unvaccinated (32/113), Omicron unvaccinated (2/8), Alpha-Delta vaccinated (4/26), and Omicron vaccinated (2/46). (C) Hospitalization due to COVID-19: prevaccination (204/358), Alpha-Delta (53/95), Omicron (2/6), Alpha-Delta vaccinated (8/25), and Omicron vaccinated (10/39). (D) COVID-19–specific therapy: prevaccination (215/363), Alpha-Delta unvaccinated (49/108), Omicron unvaccinated (2/7), Alpha-Delta vaccinated (7/22), and Omicron vaccinated (7/36). (E) Oxygen therapy requirement: prevaccination (147/367), Alpha-Delta vaccinated (39/106), Omicron vaccinated (3/7), Alpha-Delta unvaccinated (6/21), and Omicron unvaccinated (5/33). (F) ICU admission: prevaccination (29/391), Alpha-Delta unvaccinated (11/111), Omicron unvaccinated (1/8), Alpha-Delta vaccinated (1/26), and Omicron vaccinated (0/44). CFR₂₈, 28-day case fatality rate; ICU, intensive care unit.

FIG 3.

Measures of COVID-19 severity according to the vaccination status. Partially vaccinated patients were excluded. Rates of COVID-19 outcomes are calculated with 95% Wilson CIs, as events occurred for each outcome per number of patients observed in each phase, excluding missing data. Events/patients ratio is also provided. Overall missing/excluded events were: 4 CFR₂₈, 4 ICU admission, 61 hospitalization, 49 oxygen therapy requirement, 47 COVID-19 specific therapy. (A) CFR₂₈: unvaccinated patients (71/490) and vaccinated patients (3/71). (B) COVID-19 complications: unvaccinated patients (134/494) and vaccinated patients (6/72). (C) Hospitalization due to COVID-19: unvaccinated patients (253/444) and vaccinated patients (18/64). (D) COVID-19–specific therapy: unvaccinated patients (261/461) and vaccinated patients (14/59). (E) Oxygen therapy requirement: unvaccinated patients (185/463) and vaccinated patients (12/55). (F) ICU admission: unvaccinated patients (39/492) and vaccinated patients (2/71). CFR₂₈, 28-day case fatality rate; ICU, intensive care unit.