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

Goryainova AYu1,2, Usman NYu3, Rubanovich AV4, Borinskaya SA4, Mescheryakov AA5
About authors

1 Clinical Oncologic Dispensary № 1, Krasnodar, Russia

2 Kuban State Medical University, Krasnodar, Russia

3 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia

4 Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia

5 Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia

Correspondence should be addressed: Alla Yu. Goryainova
Dimitrov, 146, Krasnodar, 350040, Russia; ur.xednay@aveulehsam

About paper

Funding: medical piece of research was conducted without sponsor’s support as part of the Inter-organization agreement concerning non-profit scientific collaboration. Molecular genetic testing and statistical analysis were conducted as part of the publicly funded project “Study of Polymorphism at the Cellular, Organism and Population Levels as a Basis for Genetic Technology Development” (№ 122022600161-3).

Author contribution: Goryainova AYu — study design, data acquisition, statistical processing of the results, review of papers on the subject, manuscript writing; Usman NYu — selection of genotyping method and molecular genetic analysis; Rubanovich AV — statistical processing of the results; Borinskaya SA — literature review, molecular genetic testing, interpretation of the results, manuscript editing; Meshcheryakov AA — study concept and design, manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Blokhin National Medical Research Center of Oncology (protocol № 10 dated 26 December 2019). Anonymized patient information was acquired and processed. Personal and medical data were not subject to transfer to a third party or to disclosure in the study results. All patients submitted the informed consent to study participation.

Received: 2023-09-28 Accepted: 2023-10-20 Published online: 2023-10-29

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.

Keywords: breast cancer, tamoxifen, endometrial thickness, CYP2D6, endocrine therapy