Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women

Abstract

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population’s genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.

Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients

“…In addition, we profiled drug responserelated genomic variants, evaluated the prognostic value of the ctDNA fraction and bTMB, and assessed the ability of ctDNA to monitor disease progression. In this study, molecular profiling of ABC revealed genomic variants consistent with several previous reports, and TP53 (44.0%) and PIK3CA (28.4%) were the two most commonly altered genes [2,35,38,41,42]. TP53 is a well-characterized tumour suppressor gene that acts as a regulator of key cellular processes involved in controlling cell proliferation and maintaining genomic stability [43,44].…”

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

“…(E) When HR+ groups were stratified by clinicopathological features that increase risk of relapse, the detection rate was significantly lower in the low-risk than the high-risk group of HR+ HER2À. The HRÀ HER2À group showed the highest number of mutations per patient, consistent with the literature that triple-negative breast cancer had higher tumor mutational burden than other subtypes [21,22], making it a good candidate for immune checkpoint therapy.…”

“…Our data showed that 94.8% of the Vietnamese patients had at least one somatic mutation in the 95 cancer‐associated genes. The HR− HER2− group showed the highest number of mutations per patient, consistent with the literature that triple‐negative breast cancer had higher tumor mutational burden than other subtypes [ 21 , 22 ], making it a good candidate for immune checkpoint therapy.…”

Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer

“…Along with cells, isolated nucleic acids have also been studied for their potential role as cancer biomarkers. Several studies have evaluated circulating DNA as a predictor of treatment response, disease progression [ 94 ], shorter PFS [ 95 , 96 ], and worse patient outcomes [ 97 , 98 ]. In addition, four studies evaluated mutations and/or gene expression in ctDNA.…”