Molecular profiles and circulating tumor-DNA detected in Chinese early stage breast cancer

Jing Lan; Ye-Hui Zhou; Min-Xia Zhang; Dong-Qin Chen; Meng-Yao Wu; Zheng-Yuan Yu

doi:10.21037/gs-21-691

Molecular profiles and circulating tumor-DNA detected in Chinese early stage breast cancer

Gland Surg. 2022 Feb;11(2):319-329. doi: 10.21037/gs-21-691.

Authors

Jing Lan¹, Ye-Hui Zhou¹, Min-Xia Zhang², Dong-Qin Chen³, Meng-Yao Wu⁴, Zheng-Yuan Yu⁴

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Medical, Geneplus-Beijing, Beijing, China.
³ Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

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 (TP53; 70%), PIK3CA (40%), protooncogene MYC (35%), ERBB2 (30%), and cyclin-dependent kinase 12 (CDK12; 20%). Six (30%) patients presented with ERBB2 amplification of NGS and simultaneously were positive for human epidermal growth factor receptor 2 (HER2) of IHC. ERBB2 amplification and being HER2 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 TP53 pathway, followed by the PI3K 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 ERBB2 mutation in the non-lymph node metastasis group than the lymph node metastasis group (55.6% vs. 9.1%; P=0.049). Similarly, more patients had the CDK12 mutation in the non-lymph node metastasis group than the lymph node metastasis group (44.4% vs. 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., PIK3CA and ERBB2). 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% vs. 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.

Keywords: Circulating tumor DNA (ctDNA); early stage breast cancer; lymph node metastasis; tumor mutational burden (TMB).