Triple Negative breast cancer: Diagnosis or dustbin?


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Andrew Tutt

Guy’s & St Thomas’s NHS Foundation Trust, London, UK

Abstract

Triple Negative breast cancer: Diagnosis or dustbin?

Breast cancer comprises a diverse collection of diseases with distinct biological features and clinical behaviour. Both pre-clinical and clinical research now commonly targets specific sub-groups of breast cancer with the aim of identifying biological markers or genetic phenotypes, which reveal specific therapeutic targets or indicators of prognosis for each of these groups. Examples include the targeting of oestrogen receptor (ER) driven breast cancers with diverse endocrine therapies, and sub-group of breast cancers driven by the receptor tyrosine kinase ErbB2 (HER2) using monoclonal antibodies (e.g. trastuzumab) or the small molecule inhibitor lapatinib. These novel targeted agents are, however, of no benefit to women whose breast cancers lack ER, PR and HER2 receptors; the so called “triple negative” sub-group. Increasing knowledge of the molecular pathology of and relationships between “triple negative” and “basal-like” breast cancers reveals a complex groups of diseases with significant overlap but a lack of synonymy. Data on clinical behaviour of this sub-type will be reviewed. Initial targets considered worthy of investigation in “triple negative” and “basal-like” cancers include the following: The EGF receptor, which is expressed in more than 50% and amplified in a small proportion of these cancers; c-Kit, which is overexpressed in many of these tumours; and VEGF, given the high vascularity and angiogenesis noted in some “basal-like” cancers. Src inhibitors have also been shown to have preclinical efficacy in cell lines with a triple negative phenotype. Our group has explored the concept of targeting abnormal DNA repair associated with abnormal BRCA1 function within this breast cancer sub-type. The rationale for, and nature of, clinical trials examining targeted approaches will be discussed.