Endocrine therapy is the most effective systemic treatment for patients with hormone-receptor-positive (HR + ) breast cancer. Unfortunately, efficacy is often limited by the onset of resistance, which is almost inevitable for patients with advanced disease. Several patterns of endocrine resistance are recognizable clinically, including: A) tumors that are inherently insensitive to all attempts at estrogen receptor (ER) targeting despite expression of ER (pan-endocrine therapy resistance); B) tumors that are estrogen dependent but resistant to one or more specific endocrine therapies (agent-selective resistance); and C) tumors that initially respond but subsequently progress (acquired resistance). Current insights into the molecular basis for these resistance patterns are rudimentary, but are most clearly illuminated by investigations that focus on the crosstalk between the ErbB or HER peptide growth factor family and the ER. The data are sufficiently compelling to be addressed by ongoing clinical trials that examine combinations of endocrine agents and either trastuzumab Medicine, 660 South Euclid Avenue, Campus Box 8056, Division of Oncology, St. Louis, Missouri 63110, USA. Telephone: 314-362-8866; Fax: 314-362-7086; e-mail: mellis@im.wustl.edu Received March 26, 2004; accepted for publication April 15, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ®
LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss patterns of resistance to endocrine therapy for breast cancer.2. Relate differences in resistance patterns in early and advanced disease settings.3. Identify potential treatment strategies to overcome resistance and/or restore endocrine therapy efficacy.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.