Molecular heterogeneity in breast cancer: State of the science and implications for patient care

Rachel E. Ellsworth, Heather L. Blackburn, Craig D. Shriver, Patrick Soon-Shiong, Darrell L. Ellsworth*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

146 Scopus citations

Abstract

The identification of extensive genetic heterogeneity in human breast carcinomas poses a significant challenge for designing effective treatment regimens. Significant genomic evolution often occurs during breast cancer progression, creating variability within primary tumors as well as between the primary carcinoma and metastases. Current risk allocations and treatment recommendations for breast cancer patients are based largely on characteristics of the primary tumor; however, genetic differences between disseminated tumor cells and the primary carcinoma may negatively impact treatment efficacy and survival. In this review we (1) present current information about genomic variability within primary breast carcinomas, between primary tumors and regional/distant metastases, among circulating tumor cells (CTCs) and disseminated tumor cells (DTCs), and in cell-free nucleic acids in circulation, and (2) describe how this heterogeneity affects clinical care and outcomes such as recurrence and therapeutic resistance. Understanding the evolution and functional significance of the composite breast cancer genome within each patient is critical for developing effective therapies that can overcome obstacles presented by molecular heterogeneity.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalSeminars in Cell and Developmental Biology
Volume64
DOIs
StatePublished - Apr 2017
Externally publishedYes

Keywords

  • Breast cancer
  • Cell-free DNA
  • Circulating tumor cells
  • Intratumor heterogeneity
  • Metastasis

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