Neoadjuvant endocrine therapy and window of opportunity trials: new standards in the treatment of breast cancer?

ABSTRACT

Until recently, the use of neoadjuvant endocrine therapy was mainly restricted to those patients whose general frailty or comorbidities were contraindications to surgery. There is now increased evidence that certain patient populations (i.e. older patients with hormone-receptor positive disease) can gain as good a pathologic response, with considerably less toxicity, from neoadjuvant endocrine therapy than from neoadjuvant chemotherapy. Optimization of neoadjuvant endocrine therapy is therefore an important therapeutic goal. However, possibly of greater importance in the overall management of breast cancer, is the increased interest in exploring the effects of brief periods of endocrine therapy on in vivo biomarkers, in so called window of opportunity trials. These trials can not only be used to identify the mechanisms of action of novel agents but also to predict optimal subsequent adjuvant therapy for individual patients. While this paper will briefly review the history of neoadjuvant endocrine therapy, more emphasis will be on the evaluation of pivotal window of opportunity trials that will likely lead to a long awaited paradigm shift in the management of breast cancer.