Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony‐stimulating factor following chemotherapy: Triangulation of evidence using population‐based cohort and Mendelian randomization analyses

Abstract Recombinant human granulocyte colony‐stimulating factor (G‐CSF) administration in patients with cancer and coronavirus disease (COVID‐19) remains controversial. Concerns exist that it may worsen COVID‐19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy‐induced neutropenia (CIN) or febrile neutropenia post‐chemotherapy. Here, we determined whether prophylactic or therapeutic G‐CSF administration following chemotherapy exacerbates COVID‐19 progression to severe/critical conditions in breast cancer patients with COVID‐19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID‐19 and received G‐CSF post‐chemotherapy, with most being vaccinated pre‐chemotherapy. We prospectively observed COVID‐19‐related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G‐CSF or its associated granulocyte traits on COVID‐19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID‐19‐related hospitalization following prophylactic or therapeutic G‐CSF administration after chemotherapy. No mortality or progression to severe/critical COVID‐19 occurred after G‐CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G‐CSF and COVID‐19‐related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G‐CSF or related granulocyte traits on COVID‐19‐related hospitalization or COVID‐19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G‐CSF after chemotherapy for managing CIN in patients with breast cancer and COVID‐19 would worsen COVID‐19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID‐19 vaccination.