Zoe Huestis & Miley Nguyen, PharmD, RPh
Have YOU EVER WONDERED …how antidepressants could impact breast cancer treatment?
- Many women on tamoxifen for breast cancer treatment are co-prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs) (Desmarais et al., 2009).
- Some SSRIs are strong CYP2D6 inhibitors and may reduce tamoxifen’s effectiveness, increasing the risk of recurrence (Kelly et al., 2010)
- Pharmacogenomics (PGx) has the potential to ensure treatment success and quality of life for women facing breast cancer and mental health challenges.
The Challenge
Breast cancer ranks as the leading cancer diagnosis among women around the world (Kelly et al., 2010).
- Tamoxifen has been a standard treatment that significantly reduces the risk of recurrence and breast cancer-related mortality (Kelly et al., 2010). CYP2D6 is key to activating tamoxifen, and both genetic differences and enzyme-blocking drugs can independently affect how well the treatment works (Goetz et al., 2007).
- Depression affects up to 25% of women with breast cancer, nearly twice the rate in the general female population. Nearly half of survivors use antidepressants; 30% of those starting tamoxifen are co-prescribed antidepressants such as SSRIs, and most commonly paroxetine. As SSRIs differ in their CYP2D6 inhibition strength, stronger inhibitors can directly impact tamoxifen therapeutic outcomes (Kelly et al., 2010).
- Multiple studies have shown that paroxetine and fluoxetine strongly inhibit tamoxifen activation and may be avoided during therapy (Desmarais et al., 2009). Paroxetine, in particular, irreversibly blocks CYP2D6, significantly reducing tamoxifen effectiveness. As a result, women on both paroxetine and tamoxifen had a higher risk of breast cancer death, which increased with longer use (Kelly et al., 2010).
Benefits & Real-World Applications of PGx
Breast cancer ranks as the leading cancer diagnosis among women around the world (Kelly et al., 2010).
- Patients with reduced CYP2D6 activity, whether due to genetics or interacting medications, are less able to convert tamoxifen into its active form, increasing the risk of recurrence. In such cases, alternative hormonal therapies are strongly recommended (CPIC, 2018).
- Integrating pharmacogenomics with drug-drug interaction assessment is key to optimizing tamoxifen therapy. In patients with reduced CYP2D6 function due to genetic variation, co-administration of strong CYP2D6 inhibitors can further compromise drug activation, increasing the risk of treatment failure. Considering these fators offer more effective, and personalized care.
Conclusion
PGx helps bridge this gap by guiding treatment selection based on an individual’s genetic makeup.
- Pharmacogenomics brings a meaningful impact to breast cancer care by guiding treatment choices for women struggling with depression. Combining genetic insights into care allows for precise medication selection, reduced adverse interactions, and maximize treatment benefits
Learn more about UGenome.
Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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