EXPERIENCE OF PERSONALIZED APPOINTMENT OF NEOADJUVANT CHEMOTHERAPY FOR PATIENT WITH BREAST CANCER: A PROSPECTIVE STUDY
E.M. Slonimskaya (1, 2), P.V. Kazantseva (1), N.V. Litviakov (1, 3), M.M. Tsyganov (1), M.K. Ibragimova (1, 3), A.V. Doroshenko (1), R.U. Vernadsky (1), M.A. Vostrikova (2), N.A. Lushnikova (2)
1 Research Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia;
2 Siberian State Medical University, Tomsk, Russia;
3 National Research Tomsk State University, Tomsk, Russia
Background. One of the most significant reasons for the low effectiveness of neoadjuvant chemotherapy (NACT) of breast cancer (BC) is the lack of a personalized approach to the choice of conventional chemotherapy regimens. Objective. Development and prospective clinical testing of the algorithm for personalized administration of NACT for BC patients using molecular-genetic tumor markers. Methods. All patients participating in the study were divided into two groups. The first (study) group included 37 patients with breast cancer. In these patients, before the start of the treatment, DNA and RNA were isolated from the tumor tissue from the biopsy; representation and expression levels of ABC transporter genes and the BRCA1, Top2a, TYMS and TUBB3 sensitivity genes were determined using the CytoScan HD Array microarray (Affymetrix, USA) and quantitative PCR. Based on the results of molecular genetic analysis, the treatment tactics were personalized for patients. The second group (historical control) included 71 patients with luminal B HER2(-) breast cancer, who received NACT without taking into account the molecular genetic characteristics of the tumor. Results. The study included 108 patients with luminal HER2(-) – BC. A two-stage algorithm for the personalized assignment of NACT was developed. At the first stage, the reasonability of preoperative treatment was determined based on the markers of the ABC genes and regions 18p11.1-32; 11q21- 25 and 1q21.3-44 representation; and in the second stage, in the case of a positive results, a personalized choice of the regimen was made based on the markers of the representation and the expression of sensitivity genes. Personalized NACT was assigned to 26 of 37 patients; 11 patients started treatment with surgery, as they had no indication for chemotherapy in the preoperative period. The immediate efficacy of NACT in the study group was 88.5% (23 of 26), stabilization was observed in 5 (11.5%) patients. In the control group, the immediate efficacy of NACT was 53.5% (38 of 71), stabilization and progression were observed in 46.5% (33 of 71) patients. Differences between the groups were statistically significant (p=0.002). Conclusion. New informative predictive criteria have been determined; their use has significantly increased the efficacy of NACT in comparison with standard approaches to prescribing preoperative treatment.
About the Autors
Corresponding author: Е.М. Slonimskaya – MD, Prof., Head of the Department of General Oncology of the Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia; e-mail: email@example.com