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Molecular classification of triple negative breast cancer
Author(s) -
Lehmann Brian D,
Bauer Josh A,
Chen Steven,
Shyr Yu,
Sanders Melinda,
Pietenpol Jennifer A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.328.1
Subject(s) - triple negative breast cancer , cancer research , androgen receptor , breast cancer , estrogen receptor , biology , progesterone receptor , epithelial–mesenchymal transition , oncology , medicine , cancer , prostate cancer , metastasis , genetics
Triple negative breast cancer (TNBC) represents 10–20% of all breast cancers that lack estrogen receptor (ER) and progesterone receptor expression as well as amplification of the human epidermal growth factor receptor 2 (HER2). TNBCs more frequently affect younger and African‐American women and are more aggressive. Targeted therapies exist for ER‐positive and HER2‐amplified breast cancers, however treatment options for TNBC are limited by a lack of molecular understanding of this disease. To gain insight into the biology of TNBC, we compiled transcriptional profiles of 587 TNBCs and classified this disease into six molecular subtypes. We identified representative cell lines for each TNBC subgroup and targeted prominent signaling pathways. We identified two basal‐like subgroups characterized by cell cycle and DNA damage response genes and cell lines preferentially responded to cisplatin. Two mesenchymal‐like subgroups were enriched in differentiation, epithelial‐mesenchymal transition and growth factor pathways. We described an immunomodulatory subgroup, defined by immune cell markers and signaling genes. We identified a subgroup driven by androgen receptor (AR) signaling and PIK3CA mutations, rendering cell lines sensitive to AR antagonists and PI3K inhibitors. These data will aid in clinical trial design and biomarker selection for alignment of TNBC patients to appropriate targeted therapies.