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

## TL;DR

This study shows that CYP2D6*4 gene carriers taking tamoxifen for breast cancer have higher mortality risks, suggesting longer follow-up is needed for accurate results.

## Contribution

The study provides real-world evidence on the impact of CYP2D6*4 genotype and tamoxifen dose on breast cancer patient survival.

## Key findings

- Higher tamoxifen doses were linked to lower all-cause and breast cancer mortality.
- CYP2D6*4 heterozygotes had a 76% higher all-cause mortality risk compared to non-carriers.
- CYP2D6*4 homozygotes had an 11.6-fold higher breast cancer-specific mortality risk.

## Abstract

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.

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).

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.

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.

The online version contains supplementary material available at 10.1186/s12885-025-14162-4.