Markers of endocrine sensitivity

Endocrine therapy has been a mainstay of treatment of breast cancer since the late 1800s [1], and it has led to remarkable palliation, mortality reduction and even prevention in women with or at risk for this disease. A breast cancer can be either oestrogen independent (and therefore refractory to all endocrine treatments) or endocrine dependent but resistant to specific endocrine strategies and even to specific agents. Because endocrine therapy is expensive and may be associated with frequent bothersome and occasionally life-threatening toxicities, a marker of either absolute endocrine independence or resistance to specific therapies would be remarkably valuable in caring for women with breast cancer.Of course, the oestrogen receptor (ER) represents such a marker. ER was first identified by Jensen and colleagues [2]. Very soon afterward, McGuire and colleagues [3-5] showed that although prediction of resistance was not absolute, women with ER-negative or low metastatic breast cancers were very unlikely to respond to a variety of anti-oestrogen therapies. Subsequent meta-analyses conducted by the Early Breast Cancer Trialists' Collaborative Group (the Oxford Overview) [6] confirmed nearly complete lack of benefit from adjuvant tamoxifen in ER-negative patients. Indeed, ER is one of the few tumour markers recommended by the Tumor Marker Guidelines Committee of the American Society of Clinical Oncology for routine use in the evaluation and treatment of patients with breast cancer [7].Although it is highly unlikely that patients with ER-negative tumours will benefit from endocrine treatment, only 50% to 60% of those with ER-positive, or rich, breast cancers will. This observation raises a critical question regarding the technical and biological accuracy of ER measurement. Early assays of ER were performed using ligand (oestradiol)-binding assays (LBAs), which are technically difficult, require relatively large amounts of fresh, frozen tissue, and can be complicated by