RCMG Developed Test Systems to Predict the Effectiveness of Pre-operative Chemotherapy for the Most Aggressive Subtypes of Breast Cancer
Three genes (TTC34, LTBR and CLEC14A) have been included in the test system for predicting the effectiveness of neoadjuvant (pre-operative) chemotherapy for luminal B breast cancer subtype (TMEM132D, MYO15B). The article appeared in the high-ranking journal “Cancers” (Q1, impact factor 6,575). The work was performed within the framework of the PHP grant 18-15-00430.
Breast cancer is the leading cause of death and morbidity. According to GLOBOCAN (185 countries) in 2020, 19.3 million new cases of cancer were diagnosed, 11,7% out of these (2,261,419 cases) are breast cancer. The death rate was 684,996 per year, higher than in previous periods.
Luminal B breast cancer subtype is considered the second most common after luminal A. Luminal B cancer subtype is more likely to metastasize and has a higher risk of relapse than subtype A.
The triple negative breast cancer subtype is considered the most aggressive, it can metastasize to various organs already in the initial stages of tumour development.
The «golden standard» of treatment is neoadjuvant chemotherapy, that is, therapy prior to surgery. Its main task is to reduce the size of the tumour in order to increase the chances of carrying out an organic surgery. However, according to major clinical studies, neoadjuvant chemotherapy is effective in less than 65% of cases of luminous B and triple negative breast cancer subtypes. Obviously, doctors need reliable biomarkers that will allow them to predict before starting treatment whether it will bring the desired result.
“Pre-operative chemotherapy can lead to excessive toxic stress on the body, while the therapeutic effect is not guaranteed. We tested 73 biopsy samples of breast tumors from pre-operative chemotherapy. Then, after chemotherapy, these samples were divided into two groups: one tumour, which showed a good response to treatment, and the other tumour, which did not respond to therapy. In these two groups, we used broad-spectrum sequencing to identify 29 genes, potential biomarkers, that showed differences in methylation. DNA methylation often occurs in the early stages of tumour development, so this trait can be a reliable marker in oncology. Out of 29 genes, we’ve formed 11 test systems. These markers were then validated on an independent sample of 83 patients. Crucially, validation was carried out using a real-time quantitative PCR method available in any clinical diagnostic laboratory. As a result of validation we have formed 1 test system for luminal B and triple negative breast cancer subtypes. The first included three genes, the second – two”, - said Vladimir Sigin, the researcher of the laboratory of epigenetics of the Research Centre for Medical Genetics.
Developed in the laboratory of epigenetics at RCMG test systems can be used in any clinical diagnostic laboratory, they potentially allow predicting the response to therapy with a probability of more than 80%. Researchers have also shown for the first time that epigenetic characteristics can be used in conjunction with clinical morphological indicators such as the stage of disease, the degree of lymph node lesion for more accurate prediction of treatment effectiveness.