Molecular Profiles and Circulating Tumor-DNA Detected in Chinese Early Stage Breast Cancer

Background: With the development of gene-sequencing technology, genome biomarkers, including Erb-B2 receptor tyrosine kinase 2 (ERBB2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (pIK3CA), BReast CAncer gene 1 (BRCA1), and BReast CAncer gene 2 (BRCA2), and immunomarkers, including the tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1), have become important in the selection of treatment.

Methods: Twenty patients with early stage breast cancer who underwent surgery were enrolled in this study. Tissue samples and paired postoperative peripheral blood samples were collected and subjected to the targeted-capture sequencing of 1,021 cancer-associated genes.

Results: The most frequently altered genes were tumor protein 53 (; 70%), (40%), protooncogene (35%), (30%), and cyclin-dependent kinase 12 (; 20%). Six (30%) patients presented with amplification of NGS and simultaneously were positive for human epidermal growth factor receptor 2 () of IHC. amplification and being positive were common in breast cancer patients without lymph node metastasis (5/6, 83.3%) and those in stages IA-IIA. Most of the somatic mutations clustered in the pathway, followed by the pathway. The TMB was lower than metastatic breast cancer in our cohort, and ranged from 0 to 9.6 mut/Mb (median: 1.92 mut/Mb). Interestingly, more patients had the mutation in the non-lymph node metastasis group than the lymph node metastasis group (55.6% . 9.1%; P=0.049). Similarly, more patients had the mutation in the non-lymph node metastasis group than the lymph node metastasis group (44.4% . 0%; P=0.026). Circulating tumor deoxyribonucleic acid (ctDNA) was detected in 7 of the 20 patients (35%). Of these patients, 71.4% (5/7) were in stage I/II. In addition, no correlation was found between ctDNA detection and clinicopathological features or the driver gene mutations (e.g., and ). However, patients positive for ctDNA had a higher TMB than those negative for ctDNA when grouped according to the median TMB (1.92 mut/Mb; 85.7% . 38.5%; P=0.043).

Conclusions: This study described that genomic characteristics of Chinese early stage breast cancer, and the results showed that TMB was related to the detection of ctDNA in postoperative blood.