%0 Journal Article
%T Current and future choices in endocrine therapy
%A Matthew Ellis
%J Breast Cancer Research
%D 2007
%I BioMed Central
%R 10.1186/bcr1813
%X So why is it that endocrine therapy does not cure all cases of ER-positive breast cancer, and what are the research choices that we should be making in order to design definitive clinical trials that address this critical problem? The conventional answer to this question is that ER-positive breast cancer is a spectrum of tumour types with different patterns of somatic mutations that influence ER function and reduce the efficacy of endocrine agents [4]. The best support for this hypothesis is the now definitive conclusion that HER2 gene amplification reduces efficacy of endocrine approaches to ER-positive breast cancer. In a variety of contexts, including endocrine therapy for advanced disease, the adjuvant endocrine setting and the neoadjuvant endocrine setting, the consistent pattern of evidence demonstrates that ER-positive, HER2-positive breast cancer does poorly in comparison with ER-positive, HER2-negative disease [5]. Furthermore, treatment with trastuzumab dramatically reduces the relapse rate for these patients when combined with chemotherapy. So where will we find the next example of a somatic mutation that can be targeted in the remaining cases of poor prognosis ER-positive, HER2-negative disease? The answer to this question must evolve from a study of the breast cancer genome using techniques such as array comparative genomic hybridization and high-throughput sequencing [4].Examples of other receptor tyrosine kinase amplification events that might be relevant to the problem of endocrine therapy resistance include fibroblast growth factor receptor (FGFR)1 amplification, which appears to be relatively common in ER-positive disease (frequency about 10%) and insulin-like growth factor 1 receptor (IGF1R) amplification, which is less common (frequency <5%), but it is of considerable interest because of the new generation of therapeutic IGF1R monoclonal antibodies. Downstream of the receptor tyrosine kinases include gain-of-function mutations in the ¦Á catalytic
%U http://breast-cancer-research.com/content/9/S2/S15