Evaluation of ctDNA during primary treatment of patients with triple-negative breast cancer: scientific novelty and clinical prospects. Case report

Triple-negative breast cancer (TNBC) is the most unfavorable subtype of breast cancer. Achieving pathological complete responce (pCR) is an important prognostic factor in patients diagnosed with TNBC, as it is associated with increased overall and disease-free survival. Currently, clinical parameters and pathological examination of resection tissue after surgery are used to evaluate the effectiveness of neoadjuvant drug chemotherapy (NAC). Traditional clinical and instrumental methods used in routine practice (examination, palpation, ultrasound of the mammary glands and regional areas, mammography, and MRI of the mammary glands) often do not allow for an accurate assessment of the treatment effect. The rate of detection of complete responses may be lower with clinical and instrumental assessment of the effect compared to pathological examination. In this regard, there is growing interest in assessing the effect of NAC based on changes in circulating tumor DNA (ctDNA) levels in the blood, which is characterized by the presence of genetic alterations specific to tumor tissue, i.e., liquid biopsy. This study examines two clinical cases of TNBC, determining the dynamics of ctDNA level changes during treatment and comparing these results with the severity of pathological tumor responce after NAC. In one case, pathological complete responce was achieved, while in the second, significant residual tumor was detected. Mutations for tracking ctDNA level dynamics were selected based on bioinformatics analysis of whole-exome sequencing of tumor biopsy samples and patient’s blood. Plasma ctDNA levels were assessed using digital PCR (dPCR). We obtained quantitative results for ctDNA determination in the plasma of patients with TNBC at five points and compared the dynamics of ctDNA level changes with the results of NAC. The study discusses the possible relationship between the observed ctDNA dynamics and treatment response (achievement of complete pathological tumor regression) and the feasibility of using liquid biopsy in predicting tumor response to NAC.