Cancer Res Treat.  2024 Jan;56(1):134-142. 10.4143/crt.2023.652.

Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes

• Li X
• Li Z
• Li L
• Liu T
• Qian C
• Ren Y
• Li Z
• Chen K
• Ji D
• Zhang M
• Wang J

• KMID: 2550330
• DOI: http://doi.org/10.4143/crt.2023.652

Abstract

Purpose
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Keyword

Tamoxifen; Toremifene; CYP2D6*10 polymorphism; Breast neoplasms

Figure

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  Fig. 1. Association between CYP2D6 *10 genotypes and disease-free survival in patients who received adjuvant tamoxifen (A) or toremifene (B) treatment.

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  Fig. 2. Comparison of disease-free survival between tamoxifen (TAM) and toremifene (TOR) groups.

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  Fig. 3. Comparison of disease-free survival between toremifene (TOR) and tamoxifen (TAM) in CYP2D6*10 patients with different genotypes. (A) CYP2D6*10 C/C. (B) CYP2D6*10 C/T. (C) CYP2D6*10 T/T.

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  Fig. 4. Comparison of disease-free survival between toremifene (TOR) and tamoxifen (TAM) in CYP2D6 *10 C/T and T/T patients.

Reference

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