Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women

Endocrine therapy, developed over a century ago [1,2], remains the most effective and the most clearly targeted form of systemic therapy for breast cancer. Endocrine treatments work best in women whose tumours are positive for oestrogen receptor (ER) and/or progesterone receptor (PgR). As we continue to search for newer targeted therapies that will shrink cancers effectively with few undesired side effects, and carry out complex statistical analyses to identify predictive factors, we should not forget the first targeted cancer therapy, namely ovarian ablation (OA) for breast cancer, and the first predictive factor for treatment of any cancer, the ER.For many years adjuvant OA was used and felt to be helpful, but randomized trials were not done. Subsequently, a few small randomized trials were conducted in the 1960s and 1970s. Before the first Early Breast Cancer Trialists Collaborative Group (EBCTCG) or Oxford overview was published in 1984 [3], it was generally believed that these trials showed no benefit for OA. When the meta-analytic techniques used in the EBCTCG overview were applied to these small trials, however, it became apparent that OA was associated with a reasonably large positive effect on both disease-free survival (DFS) and overall survival (OS) in node-positive and node-negative premenopausal women [3-5].The most recent EBCTCG overview http://www.ctsu.ox.ac.uk/projects/ebctcg webcite, carried out in September 2000, included updated information on 4900 women aged under 50 years included in 15 trials of OA. Only about 1300 of these women were in trials of OA in the absence of chemotherapy, whereas more than 3500 were in trials of OA in the presence of chemotherapy. In this updated analysis there was a clear separation between the trials of OA versus no treatment in the absence of chemotherapy and trials of OA plus chemotherapy versus the same chemotherapy. In the former trials large and highly significant positive effects of OA persisted at 15 years in