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Review
. 2014 Jan;232(2):142-50.
doi: 10.1002/path.4280.

Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes

Brian D Lehmann  1 , Jennifer A Pietenpol
Affiliations
Review

Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes

Brian D Lehmann et al. J Pathol. 2014 Jan.

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that respond differentially to chemotherapy and targeted agents. The absence of high-frequency molecular alterations and a limited number of known biomarkers have limited the development of therapeutic strategies for the disease. Herein, we summarize the results of the first round of targeted therapy approaches in TNBC and discuss new preclinical strategies. Common themes emerge from the proposed strategies, such as the use of biomarkers to identify tumours with genomic instability, targeting adapted molecular states resulting from tumour suppressor loss, and targeting altered metabolic pathways.

Keywords: AR; EGFR; FGFR; INPP4B; LDHB; PHGDH; PIK3CA; PTEN; TNBCtype; TP53; VEGFR; WEE1; basal-like; genomic instability; subtypes; therapy; triple-negative breast cancer.

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Figures

Figure 1
Figure 1. Relationship between molecular TNBC subtypes and the intrinsic breast cancer subtypes
(A) Using a bimodal filter on ER, PR and HER2 expression, 374 TNBC samples were extracted from 2441 breast cancer gene expression microarray profiles originating from 14 datasets*. The TNBC samples were either normalized with all samples (left dendrogram branch) followed by PAM50 prediction for intrinsic breast subtypes or normalized alone (right dendrogram branch) followed by prediction with PAM50 (left) or TNBCtype (right). Doughnut pie charts display the relative distribution of the same 374 TNBC samples analyzed using the indicated subtype tools. (B) Pie charts represent analysis of the indicated TNBC subytpes using the PAM50 intrinsic subtype tool. Pie charts display the TNBCtype composition of either (C) basal-like or non basal- like TNBC or (D) low-claudin vs. high-claudin TNBC. Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like, and luminal AR (LAR). *(GSE1456, GSE1561, GSE2034, GSE2109, GSE2990, GSE2603, GSE5327, GSE5460, GSE5847, GSE7390, GSE11121, GSE12276, GSE18864, GSE20194)
See this image and copyright information in PMC

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