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Oncotarget. 2015 May 30;6(15):12890-908.

Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype?

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Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Oncology, Eugène Marquis Cancer Center, Rennes, France.
The University of Texas MD Anderson Women's Cancer Moons Shot Program, Houston, TX, USA.
Clinical Cancer Genetics Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.


Significant research has been conducted to better understand the extensive, heterogeneous molecular features of triple-negative breast cancer (TNBC). We reviewed published TNBC molecular classifications to identify major groupings that have potential for clinical trial development. With the ultimate aim to streamline translational medicine, we linked these categories of TNBC according to their gene-expression signatures, biological function, and clinical outcome. To this end, we define five potential clinically actionable groupings of TNBC: 1) basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2) mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem cell features; 3) immune-associated TNBC; 4) luminal/apocrine TNBC with androgen-receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we highlight the major biological pathways and discuss potential targeted therapies in TNBC that might abrogate disease progression. However, many of these potential targets need clinical validation by clinical trials. We have yet to know how we can enrich the targets by molecular classifications.


epithelial-mesenchymal transition; gene expression profiling; immunotherapy; targeted therapy; triple-negative breast cancer

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