Journal Article

Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer

Nguyen, Sao Trung, Pham, Thanh Huyen, Giang, Hoa, Nguyen, Minh Long, Nguyen Hoang, Van‐Anh, Nguyen Thi, Ngoc Thanh, Pham, Dinh Hoang, Nguyen, Hoai‐Nghia, Tu, Lan N., Doan, Phuoc Loc, Lu, Y‐Thanh, Nguyen, Ngoc Mai, Do, Thanh Thuy Thi, Phan, Minh‐Duy, Truong, Dinh Kiet, Nguyen, Du Quyen, Nguyen, Duy Sinh, Nguyen, Trieu Vu, Dinh, Thi Cuc

2023

Overview

Breast cancer is the leading cause of cancer death in Vietnamese women, but its mutational landscape and actionable alterations for targeted therapies remain unknown. After treatment, a sensitive biomarker to complement conventional imaging to monitor patients is also lacking. In this prospective multi‐center study, 134 early‐stage breast cancer patients eligible for curative‐intent surgery were recruited. Genomic DNA from tumor tissues and paired white blood cells were sequenced to profile all tumor‐derived mutations in 95 cancer‐associated genes. Our bioinformatic algorithm was then utilized to identify top mutations for individual patients. Serial plasma samples were collected before surgery and at scheduled visits after surgery. Personalized assay tracking the selected mutations were performed to detect circulating tumor DNA (ctDNA) in the plasma. We found that the mutational landscape of the Vietnamese was largely similar to other Asian cohorts, showing higher TP53 mutation frequency than in Caucasians. Alterations in PIK3CA and PI3K signaling were dominant, particularly in our triple‐negative subgroup. Using top‐ranked mutations, we detected ctDNA in pre‐operative plasma in 24.6–43.5% of the hormone‐receptor‐positive groups and 76.9–80.8% of the hormone‐receptor‐negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15‐month follow‐up revealed post‐operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis. Our personalized assay is streamlined and affordable with promising clinical utility in residual cancer surveillance. We also generated the first somatic variant dataset for Vietnamese breast cancer women that could lay the foundation for precision cancer medicine in Vietnam. The authors determine, for the first time, the somatic variant landscape of Vietnamese women with breast cancer, and establish a personalized tumor‐informed assay (K‐Track®) to detect ctDNA in liquid biopsy. This assay is streamlined and affordable, with promising clinical utilities in both residual cancer surveillance and actionable mutation profiling for breast cancer patients.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: 1-Phosphatidylinositol 3-kinase / Biomarkers / Biomarkers, Tumor - genetics / Biopsy / Blood / Breast cancer / Breast Neoplasms - pathology / circulating tumor DNA / Epidermal growth factor / Estrogens / Female / Genetic testing / Genomes / Humans / Leukocytes / Lymphatic system / Medical prognosis / Metastasis / minimal residual disease / Mutation / Mutation - genetics / mutational landscape / next‐generation sequencing / Nucleotide sequence / p53 Protein / Patients / Phosphatidylinositol 3-Kinases - genetics / Polymerase chain reaction / Precision medicine / Prospective Studies / somatic mutation / Southeast Asian People / Surgery / Tumors / Vietnam