Triple negative breast cancer (TNBC) is characterized by a lack of estrogen receptors, progesterone receptors and epidermal growth factor 2 receptors. Because of the lack of hormone receptors, triple negative breast cancers do not respond to targeted hormone therapy or HER2 therapy. Standard therapy for TNBC remains mainly limited to surgery, radiation therapy, and chemotherapy; however, newer therapies like PARP inhibitors are showing promise.
The current classification of triple negative breast cancer by a lack of receptors really tells us what this form of breast cancer is not, but does not tell us what it is. On-going research studies have been attempting to more clearly characterize triple negative breast cancer in hopes of developing personalized and targeted therapies for TNBC. One such study was recently published and is free to read online.
In this study researchers identified 587 TNBC cases and analyzed their gene expression profiles to better characterize the molecular subtypes of triple negative breast cancer. The researchers reported that they identified 6 TNBC molecular subtypes and that the subtypes had unique responses to treatments. These subtypes are briefly described below.
Basal-Like - two basal-like molecular subtypes were identified and called BL1 and BL2. These subtypes had elevated expressions of cell growth cycle genes and DNA damage response genes. These subtypes were primarily responsive to treatment with cisplatin.
Mesenchymal Type - two mesenchymal types, labeled M and MSL, were identified. These two molecular subtypes showed high gene expression patterns linked to growth factor pathways and to the epithelial-mesenchymal transition. These subtypes were mainly responsive to dasatinib and NVP-BEZ235, a specific cell kinase inhibitor.
Immunomodulatory - one immunomodulatory (IM) subtype was identified. This subtype expresses high levels of genes associated with the immune system.
Luminal Androgen Receptor - one luminal androgen receptor (LAR) TNBC subtype was identified. This subtype was characterized by a high level of androgen receptors and it was senstive to the androgen receptor blocker bicalutamide.
These results are potentially very important and could have major implications on the development of future breast cancer treatments for triple negative breast cancer. It is clear from this study, that there are distinct forms of TNBC and that each form responds differently to treatments. Additionally, the study investigators reported that each subtype of TNBC showed different rates of relapse-free survival. These results could be an important first step in truly personalizing targeted breast cancer treatments for patients with triple negative breast cancer.
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