Unveiling Pharmacogenomic Patterns in Breast Cancer Through Big Data

Area of Science:

• Genomics
• Oncology
• Personalized Medicine

Background:

• Pharmacogenomics (PGx) is crucial for personalized medicine in cancer care.
• Genetic variations influence drug efficacy and toxicity.
• CYP2D6 enzyme activity is key in metabolizing many common medications.

Purpose of the Study:

• To investigate the prevalence of CYP2D6-related medications and phenotypes in female breast cancer patients.
• To assess the impact of genetic variability on drug response in this cohort.
• To evaluate the clinical utility of pharmacogenomic data in breast cancer treatment.

Main Methods:

• Utilized genomic and electronic health record (EHR) data from 5,576 female breast cancer patients in the NIH's All of Us Research Program.
• Developed a customized pipeline to determine CYP2D6 genotypes and phenotypes.
• Analyzed prescription data for CYP2D6-metabolized drugs, including Tamoxifen, ondansetron, and tramadol.

Main Results:

• 77% of patients were prescribed at least one CYP2D6-metabolized drug.
• Actionable CYP2D6 phenotypes were identified in 12.5% of the cohort.
• Approximately 25% of phenotyped patients exhibited non-normal metabolizer types, with increased prescribing post-diagnosis.

Conclusions:

• Significant prevalence of CYP2D6-associated drugs and non-normal metabolizer phenotypes in breast cancer patients.
• Highlights the importance of pharmacogenomic considerations for optimizing treatment.
• Supports the integration of PGx guidelines into routine clinical practice for improved patient outcomes.