A CENTURY OF DECIPHERING THE CONTROL MECHANISMS OF ESTROGEN ACTION IN BREAST CANCER: THE ORIGINS OF TARGETED THERAPY AND CHEMOPREVENTION

The story of deciphering the mechanisms that control the growth of sex-hormone-dependent cancers started more than a hundred years ago. Clinical observations of the apparently random responsiveness of breast cancer to endocrine ablation (hormonal withdrawal) provoked scientific enquiry in the laboratory that resulted in the development of effective strategies for targeting therapy to the estrogen receptor (ER) (or the androgen receptor in the case of prostate cancer), the development of antihormonal treatments that dramatically enhanced patient survival, and the fi rst successful testing of agents to reduce the risk of developing any cancer. Most importantly, elucidating the receptor-mediated mechanisms of sex-steroid-dependent growth and the clinical success of antihormones has had broad implications for medicinal chemistry with the synthesis of new selective hormone receptor modulators for numerous clinical applications. Indeed, the successful translational research on the ER was the catalyst for the current strategy for developing targeted therapies for the tumor and the start of “individualized medicine.” Over the past 50 years, ideas about the value of antihormones have translated effectively from the laboratory to improvement of clinical care, increase in national survival rates and signifi cant reduction in the burden of cancer.