Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics

Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P

• UD
  U.S. Department of Energy

  Awards: -AC02-05CH11231, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
• BC
  Breast Cancer Research Foundation

  Award: CA16672
• RA
  Robert and Janice McNair Foundation
• NI
  National Institutes of Health

  Awards: CA099031, CA58223, P50-CA58223, CA16672, P50 CA58207, DE-AC02-05CH11231, U54 CA 112970, U54 CA112970, P50-CA58223-09A1
• OO
  Office of Science

  Awards: AC02-05CH11231, -AC02-05CH11231, DE-AC02
• NC
  National Cancer Institute

  Awards: P50 CA 58207, CA112970, CA16672, P50-CA58223, U54 CA 112970, DE-AC02-05CH11231, P50-CA58223-09A1, CA58223, CA58207, P50 CA58207
• LB
  Lawrence Berkeley National Laboratory

  Awards: DE-AC02-05CH11231, 05CH11231, AC02-05CH11231