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Triple negative breast cancer: unmet medical needs

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Abstract

Triple negative breast cancer (TNBC) is an aggressive clinical phenotype characterized by lack of expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence of human epidermal growth factor receptor-2 (HER2) overexpression. It shows substantial overlap with basal-type and BRCA1-related breast cancers, both of which also have aggressive clinical courses. However, this overlap is not complete, and the expression of ER, PR, and HER2 has been noted in basal-like tumors. TNBC also includes the normal-like subtype, and not all patients with TNBC harbor BRCA1 mutations. Because of its expression profile, TNBC is not amenable to treatment with hormone therapy or the anti-HER2 monoclonal antibody trastuzumab, and systemic treatment options are currently limited to cytotoxic chemotherapy. Overall survival, whether in early-stage or advanced disease, is poor compared with that in patients who have other phenotypes. A number of targeted approaches to TNBC are undergoing clinical evaluation, including the use of agents with poly(ADP-ribose) polymerase inhibitory properties such as iniparib (the United States Adopted Name for the investigational agent BSI-201), olaparib (AZD2281), and veliparib (ABT-888), antiangiogenic agents such as bevacizumab and sunitinib, and epidermal growth factor receptor blockers such as cetuximab and erlotinib. Encouraging results with some of these agents have been reported, thereby offering the promise for improved outcomes in patients with TNBC. The clinical characteristics of TNBC and clinical experience to date with novel targeted agents under development for this aggressive phenotype is reviewed.

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Nadia Harbeck, Frédérique Penault-Llorca, … Fatima Cardoso

Abbreviations

ASCO:

American Society of Clinical Oncology

CI:

Confidence interval

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor-2

HR:

Hazard ratio

IHC:

Immunohistochemical

OR:

Odds ratio

OS:

Overall survival

PARP:

Poly(ADP-ribose) polymerase

pCR:

Pathologic complete response

PIR:

PARP inhibitor-resistant

PR:

Progesterone receptor

TNBC:

Triple negative breast cancer

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Acknowledgments

The authors thank Johnathan C. Maher, Ph.D., of BlueSpark Healthcare Communications for medical and editorial assistance with this manuscript. Financial support for medical and editorial assistance was provided by Sanofi-aventis US. The authors were fully responsible for all content and editorial decisions. Dr. Childs is an employee of Sanofi-aventis US. Drs. Pegram and Pal did not receive financial support or compensation related to the development of the manuscript.

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Correspondence to Sumanta Kumar Pal.

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Pal, S.K., Childs, B.H. & Pegram, M. Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat 125, 627–636 (2011). https://doi.org/10.1007/s10549-010-1293-1

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  • DOI: https://doi.org/10.1007/s10549-010-1293-1

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