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Targeted Approaches to Triple-Negative Breast Cancer: Current Practice and Future Directions

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Abstract:

Triple-negative breast cancer (TNBC), that is breast cancer which stains negatively at immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), comprises a particularly aggressive subtype of breast cancer, with high rate of early local and distant relapse. TNBC have demonstrated sensitivity to cytotoxic treatment regimens, but in the absence of HER2, ER and PR there is no benefit from hormonal therapy or trastuzumab. The lack of known specific molecular targets has promoted abundant research in order to find possible “vulnerabilities” in TNBC and the evaluation of novel biomarkers overcoming the traditional approach based on hormonal receptors and HER2-targeted therapy is one of the priorities in breast cancer research. Drugs under investigation can be broadly subdivided into four groups: (1) Agents that create DNA damage (i.e. cisplatin, cyclophosphamide); (2) Agents that inhibit poly (ADP-ribose) polymerase (PARP); (3) Tyrosin-kinase inhibitors and monoclonal antibodies; (4) Agents that inhibit downstream signals. Several preclinical and early phase clinical trials for the treatment or management of patients with triple-negative breast tumors are underway. Nonetheless, so far the major issue to deal with when trying to provide evidence for TNBC is the small numbers of the sample in the clinical studies and the retrospective nature of most of them. Future large studies could help in defining optimal treatment strategies for TNBC, both in the advanced setting as well as in the (neo) adjuvant setting.

Keywords: (ADP-ribose) polymerase; Advanced breast cancer; HER2; Triple-negative breast cancer(TNBC); epidermal growth factor; estrogen receptor; immunohistochemistry; progesterone receptor; targeted therapy; triple-negative

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986713804999321

Publication date: February 1, 2013

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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