title: Molecular heterogeneity in breast cancer: State of the science and implications for patient care.
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.
authors: Murtha Cancer Center, Windber, PA, USA.
authors: Rachel E
authors: RE
authors: Ellsworth
authors: Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
authors: Heather L
authors: HL
authors: Blackburn
authors: Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors: Craig D
authors: CD
authors: Shriver
authors: NantWorks, Culver City, CA, USA.
authors: Patrick
authors: P
authors: Soon-Shiong
authors: Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA. Electronic address: d.ellsworth@wriwindber.org.
authors: Darrell L
authors: DL
authors: Ellsworth
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D005791:Patient Care; D023041:Xenograft Model Antitumor Assays
keywords: Breast cancer; Cell-free DNA; Circulating tumor cells; Intratumor heterogeneity; Metastasis