Evolutionary trajectories and genomic divergence in localized breast cancers after ipsilateral breast tumor recurrence
Journal
Cancers
Journal Volume
13
Journal Issue
8
Date Issued
2021
Author(s)
Wu C.-H.
Yeh H.-T.
Hsieh C.-S.
Huang C.-C.
Chung Y.-C.
Tu S.-H.
Li Y.-H.
Hou M.-F.
Abstract
The evolutionary trajectories that drive clinical and therapeutic consequences in localized breast cancers (BCs) with ipsilateral breast tumor relapse (IBTR) remain largely unknown. Analyses of longitudinal paired whole-exome sequencing data from 10 localized BC patients with IBTR reveal that, compared to primary breast tumors, homologous recombination (HR) deficiency, inactivation of the HR pathway, chromosomal instability, and somatic driver mutations are more frequent. Furthermore, three major models of evolution in IBTR are summarized, through which relative contributions of mutational signatures shift, and the subclonal diversity expansions are shown. Optimal treatment regimens are suggested by the clinically relevant molecular features, such as HR deficiency (20%) or specific alterations (30%) with sensitivity to available FDA-approved drugs. Finally, a rationale for the development of the therapeutic management framework is provided. This study sheds light on the complicated evolution patterns in IBTR and has significant clinical implications for future improvement of treatment decisions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Actionability; Alteration; Clonal architecture; Ipsilateral breast tumor relapse; Whole-exome sequencing
SDGs
Other Subjects
tumor marker; adult; aged; algorithm; Article; breast cancer; cancer growth; cancer localization; cancer recurrence; chromosomal instability; clinical article; clinical feature; cohort analysis; evolution; genetic variability; homologous recombination; human; human epidermal growth factor receptor 2 positive breast cancer; human tissue; ipsilateral breast tumor relapse; middle aged; molecular cloning; sensitivity analysis; somatic mutation; triple negative breast cancer
Publisher
MDPI AG
Type
journal article