Dataset Information

Clinical factors associated with circulating tumor DNA (ctDNA) in primary breast cancer.

ABSTRACT: Noninvasive circulating tumor DNA (ctDNA) can be used to predict breast cancer recurrence and prognosis. In this study, we detected 226 and 114 somatic variants in tumor DNA from 70 primary breast cancer (PBC) patients (98.59%) and ctDNA from 48 patients (67.61%), respectively. Gene frequencies of tumor DNA and ctDNA significantly correlated (R2 = 0.9532, P < 0.0001), and tumor-derived variants were detectable in the blood of 43 patients. ctDNA was more often detected in locally advanced/metastatic and nonluminal patients. Multivariate analysis revealed that individual N stage (P < 0.001) and hormone receptor (HR) status (P = 0.001) could independently predict the detectability of tumor-derived mutations in blood. The maximal variant allele frequency of ctDNA was significantly higher in patients with stage IV/M1 (P = 0.0136) and stage T3/T4 (P = 0.0085) cancers. Finally, clonal variants in tumor DNA were more easily traced in ctDNA than subclonal variants (84.62% vs 48.75%). In conclusion, ctDNA fragments concordant with tumor DNA can be consistently detected in the majority of tested PBC patients, which may enable noninvasive genomic profiling of PBC, particularly for patients with advanced-stage tumors and positive HR status.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6487710 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical factors associated with circulating tumor DNA (ctDNA) in primary breast cancer.

Zhou Yidong Y Xu Yaping Y Gong Yuhua Y Zhang Yanyan Y Lu Yaping Y Wang Changjun C Yao Ru R Li Peng P Guan Yanfang Y Wang Jiayin J Xia Xuefeng X Yang Ling L Yi Xin X Sun Qiang Q

Molecular oncology 20190206 5

Noninvasive circulating tumor DNA (ctDNA) can be used to predict breast cancer recurrence and prognosis. In this study, we detected 226 and 114 somatic variants in tumor DNA from 70 primary breast cancer (PBC) patients (98.59%) and ctDNA from 48 patients (67.61%), respectively. Gene frequencies of tumor DNA and ctDNA significantly correlated (R<sup>2 </sup> = 0.9532, P < 0.0001), and tumor-derived variants were detectable in the blood of 43 patients. ctDNA was more often detected in locally adva ...[more]

PMID: 30672098

Similar Datasets

Project description:Breast cancer is an extremely heterogeneous disease. This heterogeneity can be observed at multiple levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Many studies have shown that the tumor microenvironment also plays a critical role in cancer initiation and progression. Although genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer outcome by identifying gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer--related pathways and processes, relatively little is known about the influence of of heterogeneity in the tumor microenvironment on these factors. We show that gene expression in the breast tumor microenvironment is highly heterogeneous, identifying at least six different classes of tumor stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma--derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodeling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer . This further demonstrates an important role for the tumor microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome.

Dataset Information

Clinical factors associated with circulating tumor DNA (ctDNA) in primary breast cancer.

Publications

Clinical factors associated with circulating tumor DNA (ctDNA) in primary breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure