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Evolutionary Trajectories and Genomic Divergence in Localized Breast Cancers after Ipsilateral Breast Tumor Recurrence.

Chia-Hsin WuHsien-Tang YehChia-Shan HsiehChi-Cheng HuangAmrita ChattopadhyayYuan-Chiang ChungShih-Hsin TuYung-Hua LiTzu-Pin LuLiang-Chuan LaiMing-Feng HouKing-Jen ChangMong-Hsun TsaiEric Y Chuang
Published in: Cancers (2021)
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.
Keyphrases
  • genome wide
  • copy number
  • depressive symptoms
  • clinical trial
  • dna damage
  • dna repair
  • healthcare
  • dna methylation
  • electronic health record
  • free survival
  • young adults
  • single cell
  • drug induced
  • health insurance