The influence of polymorphism of genes associated with breast cancer on the effectiveness of drug antitumor therapy
Authors: Goncharova T. G. , Omarbaeva N. A. , Kaydarova D. R. , Abdrakhmanova A. Zh. , Smagulova K. K. , Orazgalieva M. G. , Shatkovskaya O. V. , Malysheva L. A. , Zkrina A. М. , Dushimova Z. D. 
Published: July 2024

Background. Increasing the survival rate of breast cancer patients is a problem all over the world and directly depends on the early detection of a malignant tumor. Genome-wide associative studies (GWAS) as a minimally invasive method may be used in determining risk of breast cancer or detection at an early stage. The increase in the number of patients with disseminated breast cancer in the Republic of Kazakhstan makes it necessary to search for molecular genetic markers of breast cancer for their use in the diagnosis and treatment of patients with this pathology.

Aim. To retrospectively estimate the correlation of the effectiveness of drug antitumor therapy for breast cancer with gene polymorphism.

Materials and methods. The study included the results of genotyping biomaterial samples on high-density DNA chips (venous blood of 1,277 Kazakh patients (in the third generation) with a verified diagnosis of breast cancer with locally advanced and disseminated breast cancer who received anticancer therapy), clinical data of patients, data on the clinical efficacy and toxicity of drug therapy. GWAS data (genotypes) associated with identified responses to chemotherapy drugs were compared with similar data recorded in international databases.

Results. The family history study showed 16.52 % of women in the questionnaires had a family history of various types of ESR, and 86.25 % of them had a burden of breast cancer in women of the first degree of kinship. The average age of patients with breast cancer was 48.79 ± 11.44 years. According to the TNM classification, cancer in situ was detected in 4.78 % of patients, stage I of the disease was recorded in 15.27 %, stage II in 63.43 %, stage III in 12.60 %, stage IV in 3.92 % of patients. The vast majority of the patients (96.9 %) had a nodular form of breast cancer. The distribution of the patients by tumor phenotype: luminal type A was found in 20.4 % of patients, luminal type B in 38.3 %, luminal type B with HER2 overexpression in 14.3 %, HER2 positive form in 11.9 % of cases, 12.4 % of patients had an aggressive form – triple negative breast cancer. 18 main genotypes were identified in the Kazakh population as a result of the analysis of associations of the effectiveness of neoadjuvant chemotherapy (its individual components, according to chemotherapy regimens) and individual gene polymorphisms.

Conclusion. An associative relationship between different types of gene polymorphism and the characteristics of response to various chemotherapeutic drugs used in the treatment of breast cancer has been confirmed. The obtained results formed the basis for the development of recommendations for making changes to the clinical practice of the Republic of Kazakhstan in order to use them in identifying a genetic predisposition to breast cancer and the effectiveness of drugs used in treatment.