Breast Cancer Research and Treatment

, Volume 125, Issue 3, pp 627–636 | Cite as

Triple negative breast cancer: unmet medical needs

  • Sumanta Kumar Pal
  • Barrett H. Childs
  • Mark Pegram
Review

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.

Keywords

Breast cancer Triple negative Phenotype Basal-like BRCA1 Targeted therapy 

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

Supplementary material

10549_2010_1293_MOESM1_ESM.doc (110 kb)
Supplementary material 1 (DOC 109 kb)
10549_2010_1293_MOESM2_ESM.pdf (71 kb)
Supplementary material 2 (PDF 70 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Sumanta Kumar Pal
    • 1
  • Barrett H. Childs
    • 2
  • Mark Pegram
    • 3
  1. 1.Department of Medical Oncology and Experimental Therapeutics, Division of Genitourinary MalignanciesCity of Hope Comprehensive Cancer CenterDuarteUSA
  2. 2.Sanofi-aventis USBridgewaterUSA
  3. 3.Division of Hematology/OncologyUniversity of Miami Sylvester Comprehensive Cancer Center, University of Miami Miller School of MedicineMiamiUSA

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