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How do I Treat “Triple-Negative” Disease

  • Breast Cancer (Carla I. Falkson, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Over the recent years, there has been an increasing recognition that triple-negative breast cancer constitutes a separate, albeit heterogeneous, entity arising from distinct oncogenic pathways. Despite its aggressive clinical behavior, triple-negative disease responds favorably to cytotoxic chemotherapy resulting in high response rates. Nonetheless, the relapse rates are high and, in the absence of targeted therapies to significantly alter its natural history, the prognosis can be poor. Most of the trials conducted in the past that led to the formulation of the current guidelines have indiscriminately lumped triple-negative disease with receptor-positive subtypes. Therefore, there are relatively scant data regarding how standard approaches specifically apply for triple-negative disease. By virtue of its chemosensitive nature and high probability of achieving a complete pathologic response, neoadjuvant chemotherapy in early-stage/operable and locally-advanced/inoperable triple-negative disease is highly recommended. The indications for adjuvant chemotherapy are the same as in receptor-positive tumors, although endocrine therapies or agents targeting Her2 signaling have no established role in triple-negative disease. The optimal chemotherapy is not entirely clear; however, by virtue of their efficacy in breast cancer in general, anthracycline-containing regimens are the most widely used. The incorporation of taxanes in the regimen is supported by retrospective analyses. There is scant evidence to recommend any particular agent in the metastatic setting, although the combination of ixabepilone with capecitabine was shown to be active specifically in triple-negative disease. Given the uncertainty in the optimal management of triple-negative disease, the shortcomings of contemporary regimens, and the strong rationale of novel therapies, participation in clinical trials should be strongly considered at any stage of the disease.

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Abbreviations

ASCO:

American Society of Clinical Oncology

BRCA1 :

Breast cancer 1 early onset

BRCA2 :

Breast cancer 2 early onset

CAP:

College of American Pathologists

DNA:

Deoxyribonucleic acid

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

Her2 (ERBB2):

Epidermal growth factor receptor 2

mTOR:

Mammalian target of rapamycin

PARP:

Poly (Adenosine Diphosphate–Ribose) Polymerase

pCR:

Pathologic complete response

PI3K:

Phosphatidylinositol 3-kinase

PR:

Progesterone receptor

RNA:

Ribonucleic acid

TBCRC:

Translational Breast Cancer Research Consortium

TRAIL:

Tumor necrosis factor-related apoptosis inducing ligand

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Comprehensive Cancer Center, University of Alabama at Birmingham, NP 2540, 1530 3rd Avenue South, Birmingham, AL, 35294-3300, USA

    Christos Vaklavas MD & Andres Forero-Torres MD

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  1. Christos Vaklavas MD
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  2. Andres Forero-Torres MD
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Correspondence to Andres Forero-Torres MD.

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Level of Evidence

I: Evidence comes from multiple well-designed clinical trials conducted in representative populations with consistent results.

II: Evidence comes from at least one well-designed clinical study. Strength of evidence limited by the number, quality, or consistency of the individual studies.

III: Evidence comes from well-designed nonrandomized single-group or single-cohort studies or case–control studies. Evidence also comes from retrospective analyses of prospective clinical trials.

IV: Evidence comes from well-designed nonexperimental studies such as comparative correlational, and descriptive studies.

V: Evidence comes from case reports or case series and therefore, is insufficient for recommendations.

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Vaklavas, C., Forero-Torres, A. How do I Treat “Triple-Negative” Disease. Curr. Treat. Options in Oncol. 12, 369–388 (2011). https://doi.org/10.1007/s11864-011-0168-y

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