New Strategies in Estrogen Receptor―Positive Breast Cancer

• Published in: Clinical cancer research Vol. 16; no. 7; pp. 1979 - 1987
• Main Author: JOHNSTON, Stephen R. D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2010
• Subjects: Antineoplastic agents; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - therapy; Carcinoma - diagnosis; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - therapy; Combined Modality Therapy; Drug Resistance, Neoplasm - genetics; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical Oncology - trends; Medical sciences; Models, Biological; Pharmacology. Drug treatments; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Tumors; Mammary gland diseases; Estrogen receptor; Breast disease; Breast cancer; Malignant tumor; Research and development; Cancer; Hormonal receptor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-09-1823

Endocrine therapy has led to a significant improvement in outcomes for women with estrogen receptor-positive (ER+) breast cancer. Current questions in the adjuvant setting include the optimal duration of endocrine therapy, and the accurate molecular prediction of endocrine responsiveness using gene array-based assays compared with ER expression itself. In advanced disease, novel selective estrogen receptor antagonists (SERM) have failed to make an impact, although the pure ER antagonist fulvestrant may have a role, albeit optimal dose and sequence remain unclear. Overcoming de novo or acquired endocrine resistance remains critical to enhancing further the benefit of existing endocrine therapies. Recent progress has been made in understanding the molecular biology associated with acquired endocrine resistance, including adaptive "cross-talk" between ER and peptide growth factor receptor pathways such as epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2). Future strategies that are being evaluated include combining endocrine therapy with inhibitors of growth factor receptors or downstream signaling pathways, to treat or prevent critical resistance pathways that become operative in ER+ tumors. Preclinical experiments have provided great promise for this approach, although clinical data remain mixed. Enriching trial recruitment by molecular profiling of different ER+ subtypes will become increasingly important to maximize additional benefit that new agents may bring to current endocrine therapies for breast cancer.