Although
triple negative breast cancers (TNBC) are the most aggressive subtype of
breast cancer, they currently lack targeted
therapies. Because this classification still includes a heterogeneous collection of
tumors, new tools to classify TNBCs are urgently required in order to improve our prognostic capability for high risk patients and predict response to
therapy. We previously defined a gene expression signature, RKIP Pathway
Metastasis Signature (RPMS), based upon a
metastasis-suppressive signaling pathway initiated by
Raf Kinase Inhibitory
Protein (RKIP). We have now generated a new BACH1 Pathway
Metastasis gene signature (
BPMS) that utilizes targets of the
metastasis regulator BACH1. Specifically, we substituted experimentally validated target genes to generate a new BACH1 metagene, developed an approach to optimize patient
tumor stratification, and reduced the number of signature genes to 30. The
BPMS significantly and selectively stratified
metastasis-free survival in basal-like and, in particular, TNBC patients. In addition, the
BPMS further stratified patients identified as having a good or poor prognosis by other signatures including the Mammaprint® and Oncotype® clinical tests. The
BPMS is thus complementary to existing signatures and is a prognostic tool for high risk ER-HER2- patients. We also demonstrate the potential clinical applicability of the
BPMS as a single sample predictor. Together, these results reveal the potential of this pathway-based
BPMS gene signature to identify high risk TNBC patients that can respond effectively to targeted
therapy, and highlight
BPMS genes as novel
drug targets for therapeutic development.