CYP2D6*3, *4, *6 genotypes and endometrial thickness in patients with breast cancer during tamoxifen therapy

Tamoxifen therapy results in endometrial thickening in some patients with hormone-sensitive breast cancer (HSBC). The data on the impact of polymorphic variants of the CYP2D6 gene encoding the CYP2D6 enzyme of the cytochrome P450 family on the efficacy and safety of treatment with tamoxifen are controversial. A prospective cohort study was aimed to explore the association of CYP2D6*3, *4, *6 polymorphisms with the risk of endometrial thickness during adjuvant tamoxifen therapy for HSBC. A total of 145 patients with resectable HSBC, who received 20 mg of oral tamoxifen per day, were enrolled. The CYP2D6*3, *4, *6 polymorphisms were identified by real-time PCR. Endometrial thickness was measured by ultrasonography after 3, 6 and 9 months of endocrine therapy. The study showed that endometrial hyportrophy was more often found in patients having no alternative alleles after 3 months of follow-up (40% against 23.2% in the group of “poor” metabolizers; p = 0.034). Meta-analysis of all follow-up periods has revealed that “normal” metabolizers show a significantly higher rate of endometrial thickness than “poor” metabolizers (OR = 1.88; 95% CI = 1.27–2.79; p = 0.002). A lack of significant differences in indicators of the state of endometrium between groups of patients with different CYD2D6 genotypes and menopausal status requires further investigation.