Genotypic variations of the CYP2D6 gene in patients with breast cancer treated with tamoxifen: case series

Abstract Tamoxifen plays a key role in hormone therapy for patients with breast cancer. However, studies have reported inconsistent responses to the drug because of different factors. Among these, allelic variants of cytochrome P450 genes are important. This study aims to determine the polymorphic variants of CYP2D6 gene in patients with breast cancer who underwent tamoxifen hormone therapy, classifying them according to their phenotypes as poor, intermediate, extensive, or ultrarapid metabolizers and describing clinical outcomes, such as time to relapse and overall survival (OS). This was a case series study conducted in 47 patients diagnosed with breast cancer, between 2015 and 2018. Whole-blood samples were collected, and DNA was extracted. CYP2D6 gene alterations were assessed. The mean age was 61 ± 11 years. Ductal carcinoma occurred in 85%, of which 42% was grade 2. The predominant stages of breast cancer were IIB in 26% and stage I in 32%. Extensive phenotype metabolizers were identified in 92%, poor in 6%, and intermediate in 2% of participants. Relapse was reported in 30% of participants, with metastatic relapse in 86%, which was more frequently identified in poor metabolizers. The OS at 5 and 10 years was 91%, regardless of phenotype. OS was 90% at 5 and 10 years for extensive metabolizers. Although the sample size was very small to make significant comparisons, it was observed that both poor and extensive metabolizing patients experienced some form of relapse. The OS of patients with the extensive metabolizer phenotype in this study is similar to that reported worldwide.