Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.
Hiroji IwataYoshiko UmeyamaYuan LiuZhe ZhangPatrick SchnellYuko MoriOlivia FletcherJean-Claude MarshallJillian G JohnsonLinda S WoodMasakazu ToiRichard S FinnNicholas C TurnerCynthia Huang BartlettMassimo CristofanilliPublished in: The oncologist (2021)
Palbociclib plus endocrine therapy improves hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer outcomes, but is commonly associated with neutropenia. Genetic variants in ABCB1 may influence palbociclib exposure, and in ERCC1 are associated with chemotherapy-induced severe neutropenia. Here, the associations of single nucleotide polymorphisms in these genes and baseline characteristics with neutropenia were assessed. Low baseline absolute neutrophil count was a strong risk factor (p < .0001) for grade 3/4 neutropenia. There was a trend indicating that ABCB1_rs1128503 and ERCC1_rs11615 were potential risk factors (p < .10) for grade 3/4 neutropenia in non-Asian patients. Pharmacogenetic testing could inform clinicians about the likelihood of severe neutropenia with palbociclib.
Keyphrases
- chemotherapy induced
- risk factors
- epidermal growth factor receptor
- end stage renal disease
- metastatic breast cancer
- endothelial cells
- newly diagnosed
- stem cells
- chronic kidney disease
- ejection fraction
- advanced non small cell lung cancer
- type diabetes
- prognostic factors
- oxidative stress
- gene expression
- adipose tissue
- mesenchymal stem cells
- risk assessment
- skeletal muscle
- cell therapy
- human health
- dna damage
- induced pluripotent stem cells
- peripheral blood
- climate change
- patient reported outcomes
- pluripotent stem cells