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Different subtypes of triple-negative breast cancer respond to different therapies
Date:6/27/2011

rgeted to HER2 like trastuzumab (Herceptin).

Postdoctoral fellows Brian Lehmann, Ph.D., and Joshua Bauer, Ph.D., along with biostatistician Xi (Steven) Chen, Ph.D., identified 587 cases of TNBC among 21 publicly-available breast cancer data sets. They then analyzed the genomic data to uncover unique gene expression profiles (sets of genes that are either turned "up" or "down" in the tumors).

Their analysis revealed six distinct subtypes two "basal-like" types (BL1 and BL2) involving cell cycle and DNA damage response genes; two "mesenchymal" types (M and MSL) driven by genes involved in cell differentiation and growth factor pathways; an "immunomodulatory" (IM) group, driven by immune system genes; and a "luminal" subgroup (LAR) driven by androgen (or "male" sex hormone) signaling.

The researchers also identified cell lines representing each of these subtypes and tested various chemotherapies in development or in clinical investigation in the cell lines. They also implanted these cells into mice to generate animal models of these tumor subtypes.

They found that the basal-like subtypes (BL1 and BL2) responded to cisplatin; the mesenchymal-like subtypes (M and MSL) responded to dasatinib and experimental drug NVP-BEZ235; and the LAR subtypes were sensitive to bicalutamide.

The findings provide a way of distinguishing molecular differences in this diverse group of breast cancers and suggest molecular targets for each subtype that may inform drug discovery and development efforts.

"In our opinion, the big breakthrough is just being able to say 'this isn't one disease,'" said Pietenpol.

Being able to distinguish distinct biological subtypes of TNBC could help guide the design of select clinical trials for subtypes of breast cancer, point toward new biomarkers for patient selection for a given therapy, and identify new targets for drug discovery, she said.

"This really is the first step in translating genomic information int
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Contact: Dagny Stuart
dagny.stuart@Vanderbilt.Edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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