Current Understanding of Endocrine Therapy for Breast Cancer

Historically the endocrine therapy of breast cancer originated from a novel concept proposed by George Thomas Beaston, a surgeon in Glasgow. In 1896, he published a paper about the successful treatment of a premenopausal woman with recurrent breast cancer by bilateral oophorectomy. Actually, the principal hormone of the ovary, estrogen, was identified in 1923. Thereafter, many efforts were made to prevent estrogen production by means of radiation to ovaries, bilateral adrenalectomy, or hypophysectomy. Endocrine therapy experienced a step change in the 1960's when the estrogen receptor (ER) was discovered. This led to the elucidation of the mechanisms of estrogen action and established ER as a new target of endocrine therapy. Tamoxifen, the first selective ER modulator (SERM), has been the gold standard in the endocrine therapy of breast cancer since the drug had first been approved in the 1970s for the treatment of advanced breast cancer in the UK and the USA. Over the last 8 years, tamoxifen has been considered to be the main means of reducing mortality from breast cancer in western countries.(1) The impact of endocrine therapy for breast cancer was confirmed by the 1995 Oxford overview.(2) Recently, new endocrine agents with various action mechanisms, such as the third-generation of aromatase inhibitors, and ER downregulators, revealed equivalent or better results in the treatment of breast cancer as tamoxifen. The 7th International Conference on Adjuvant Therapy of Primary Breast Cancer held at St. Gallen, Switzerland, also recognized the increased role of endocrine therapy in properly selected patients groups, especially in younger patients with ER-positive tumors.(3) At present, numerous trials are ongoing to determine optimal endocrine therapy for breast cancer. In addition, recent advances in research upon estrogen and ER function at the molecular level have provided new strategies and a better understanding of endocrine therapy for breast cancer. Accordingly, in this review, we have attempted to summarize the basic concepts of Current Understanding of Endocrine Therapy for Breast Cancer