Evolutionary trajectories and genomic divergence in localized breast cancers after ipsilateral breast tumor recurrence

Chia Hsin Wu, Hsien Tang Yeh, Chia Shan Hsieh, Chi Cheng Huang, Amrita Chattopadhyay, Yuan Chiang Chung, Shih Hsin Tu, Yung Hua Li, Tzu Pin Lu, Liang Chuan Lai, Ming Feng Hou, King Jen Chang, Mong Hsun Tsai, Eric Y. Chuang

研究成果: 雜誌貢獻文章同行評審

摘要

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.
原文英語
文章編號1821
期刊Cancers
13
發行號8
DOIs
出版狀態已發佈 - 4月 2 2021

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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