title: Aromatase, aromatase inhibitors, and breast cancer.
abstract: Estrogens are known to be important in the growth of breast cancers in both pre and postmenopausal women. As the number of breast cancer patients increases with age, the majority of breast cancer patients are postmenopausal women. Although estrogens are no longer made in the ovaries after menopause, peripheral tissues produce sufficient concentrations to stimulate tumor growth. As aromatase catalyzes the final and rate-limiting step in the biosynthesis of estrogen, inhibitors of this enzyme are effective targeted therapy for breast cancer. Three aromatase inhibitors (AIs) are now FDA approved and have been shown to be more effective than the antiestrogen tamoxifen and are well tolerated. AIs are now a standard treatment for postmenopausal patients. AIs are effective in adjuvant and first-line metastatic setting. This review describes the development of AIs and their current use in breast cancer. Recent research focuses on elucidating mechanisms of acquired resistance that may develop in some patients with long term AI treatment and also in innate resistance. Preclinical data in resistance models demonstrated that the crosstalk between ER and other signaling pathways particularly MAPK and PI3K/Akt is an important resistant mechanism. Blockade of these other signaling pathways is an attractive strategy to circumvent the resistance to AI therapy in breast cancer. Several clinical trials are ongoing to evaluate the role of these novel targeted therapies to reverse resistance to AIs. Article from the special issue on 'Targeted Inhibitors'.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, and the Greenebaum Cancer Center, Baltimore, MD 21201, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Chumsri
authors.forename: Timothy
authors.initials: T
authors.lastname: Howes
authors.forename: Ting
authors.initials: T
authors.lastname: Bao
authors.forename: Gauri
authors.initials: G
authors.lastname: Sabnis
authors.forename: Angela
authors.initials: A
authors.lastname: Brodie
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004967:Estrogens; D011960:Receptors, Estrogen; D001141:Aromatase; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D000068878:Trastuzumab