Projects per year
Abstract
Abstract
Aim
To investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.
Method
We retrospectively included 3218 female patients who initiated tamoxifen following a diagnosis of breast cancer with long-term follow-up (median 7.5 years). A subgroup analysis of 303 genotyped patients with a median follow-up of 9.7 years was also conducted. The outcomes of interest were overall survival (OS) and breast-cancer specific survival (BCS).
Results
In the whole cohort, an additional 20 mg of tamoxifen during six-month duration was associated with a 1.6% reduction in all-cause mortality (HR: 0.984, 95% CI: 0.982–0.985, P<0.001) and a 1.9% decrease in breast cancer mortality (HR: 0.981, 95% CI: 0.979–0.984, P<0.001). In the genotyped subgroup, CYP2D6*4 heterozygotes had a 76% greater risk of all-cause mortality than *4 non-carriers (HR: 1.76, 95% CI: 1.07–2.9, P=0.025). For breast cancer-specific mortality, CYP2D6*4 heterozygotes and homozygotes had increased risk by 3.7-fold (HR: 3.7, 95% CI: 1.32–10.6, P=0.01) and 11.6-fold (HR: 11.6, 95% CI: 1.3–103.5, P=0.03), respectively.
Conclusion
Our study demonstrates that carriers of CYP2D6*4 have a higher risk of both all-cause and breast cancer-specific mortality and indicates that longer follow-up time may be crucial to determining impact. The shorter follow-up in previous studies may be a key reason for the conflicting results. A large real-world pharmacogenomic study with long-term follow-up is warranted to determine the impact of CYP2D6 genotyping and its implications for clinical decision making
Aim
To investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.
Method
We retrospectively included 3218 female patients who initiated tamoxifen following a diagnosis of breast cancer with long-term follow-up (median 7.5 years). A subgroup analysis of 303 genotyped patients with a median follow-up of 9.7 years was also conducted. The outcomes of interest were overall survival (OS) and breast-cancer specific survival (BCS).
Results
In the whole cohort, an additional 20 mg of tamoxifen during six-month duration was associated with a 1.6% reduction in all-cause mortality (HR: 0.984, 95% CI: 0.982–0.985, P<0.001) and a 1.9% decrease in breast cancer mortality (HR: 0.981, 95% CI: 0.979–0.984, P<0.001). In the genotyped subgroup, CYP2D6*4 heterozygotes had a 76% greater risk of all-cause mortality than *4 non-carriers (HR: 1.76, 95% CI: 1.07–2.9, P=0.025). For breast cancer-specific mortality, CYP2D6*4 heterozygotes and homozygotes had increased risk by 3.7-fold (HR: 3.7, 95% CI: 1.32–10.6, P=0.01) and 11.6-fold (HR: 11.6, 95% CI: 1.3–103.5, P=0.03), respectively.
Conclusion
Our study demonstrates that carriers of CYP2D6*4 have a higher risk of both all-cause and breast cancer-specific mortality and indicates that longer follow-up time may be crucial to determining impact. The shorter follow-up in previous studies may be a key reason for the conflicting results. A large real-world pharmacogenomic study with long-term follow-up is warranted to determine the impact of CYP2D6 genotyping and its implications for clinical decision making
| Original language | English |
|---|---|
| Journal | BMC Cancer |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jun 2025 |
Keywords / Materials (for Non-textual outputs)
- Tamoxifen, Breast Cancer, CYP2D6, CYP2D6*4, CYP2D6 inhibitors, SSRIs, Survival, Pharmacogenomics, Germline, Real-world
Fingerprint
Dive into the research topics of 'Clinical and pharmacogenomic predictors of survival in tamoxifen treated breast cancer female patients: a real-world study'. Together they form a unique fingerprint.-
Generation Scotland: NextGenScot
Sudlow, C. (Principal Investigator) & Deary, I. (Co-investigator)
1/11/19 → 30/04/26
Project: Research
-
Stratifying Resilience and Depression Longitudinally
McIntosh, A. (Principal Investigator), Deary, I. (Co-investigator), Evans, K. (Co-investigator), Haley, C. (Co-investigator) & Porteous, D. (Co-investigator)
1/01/15 → 30/06/21
Project: Research
-
Generation Scotland
Porteous, D. (Principal Investigator)
UK central government bodies/local authorities, health and hospital authorities
1/04/11 → 31/03/14
Project: Research