Markers of sensitivity, dependence and resistance to endocrine therapy for breast cancer

Owing to its efficacy and relative lack of toxicities, endocrine therapy is a major treatment modality for breast cancer. However, resistance and the inability to accurately predict response are obstacles to optimal management. There is a need to identify markers of clinical response and elucidate mechanisms of resistance. In this article, evidence will be presented demonstrating that: discovery of predictive markers is dependent upon the approach employed and the application required; and mechanisms of resistance are diverse and not simply mirror images of response. Different information may be obtained according to assessment read outs and type of analysis. Tumors respond to endocrine therapy in a variety of ways and a range of end points can be used to monitor hormone dependence, sensitivity and resistance to treatment. Different forms of endocrine therapies may have differing mechanisms of action - hence, markers of sensitivity/response can vary between treatments and there may be correspondingly differing mechanisms of resistance.