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Aim <p>To investigate the impact of tamoxifen dose, <i>CYP2D6</i> inhibitors, <i>CYP2D6*4</i> genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.</p> Method <p>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).</p> Results <p>In the whole cohort, an additional 20&#xa0;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, <i>P</i> &lt; 0.001) and a 1.9% decrease in breast cancer mortality (HR: 0.981, 95% CI: 0.979–0.984, <i>P</i> &lt; 0.001). In the genotyped subgroup, <i>CYP2D6*4</i> heterozygotes had a 76% greater risk of all-cause mortality than *4 non-carriers (HR: 1.76, 95% CI: 1.07–2.9, <i>P</i> = 0.025). For breast cancer-specific mortality, <i>CYP2D6*4</i> heterozygotes and homozygotes had increased risk by 3.7-fold (HR: 3.7, 95% CI: 1.32–10.6, <i>P</i> = 0.01) and 11.6-fold (HR: 11.6, 95% CI: 1.3–103.5, <i>P</i> = 0.03), respectively.</p> Conclusion <p>Our study demonstrates that carriers of <i>CYP2D6*4</i> 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 <i>CYP2D6</i> genotyping and its implications for clinical decision making.</p>

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Clinical and pharmacogenomic predictors of survival in tamoxifen treated breast cancer female patients: a real-world study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月1日

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  • Abdullah R. Al-Matrafi,
  • Khaled F. Bedair,
  • Sundararajan Srinivasan,
  • Colin Palmer,
  • Archie Campbell,
  • Caroline Hayward,
  • Ewan R. Pearson,
  • Russell D. Petty

摘要

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.