Origin and characteristics of adverse events in aromatase inhibition therapy for breast cancer.
Estrogen is critical in the progression and probably also in the initiation of breast tumors. Two classes of pharmacologic agents currently used in the treatment of estrogen receptor-positive breast tumors are the selective estrogen receptor modulators such as tamoxifen that block the interaction of estrogen with its cognate receptor, and the aromatase inhibitors (AIs) that block the final enzymatic step in the estrogen biosynthetic pathway. Recent data from first-line phase III trials in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer suggest that AIs are at least equivalent to or more effective than tamoxifen in this setting. As a result AIs are being evaluated in the adjuvant setting and may eventually displace tamoxifen as the endocrine therapy of choice for postmenopausal patients with breast cancer. Among the side effects of therapy that were observed in metastatic trials, AIs have shown less vascular and uterine adverse events than tamoxifen. Some concern exists, however, regarding their effect on lipid metabolism and bone turnover. To be acceptable for adjuvant treatment, AIs will have to show not only an advantage in efficacy, but also that any concerns from potential side effects may be managed appropriately. This article reviews the safety profile of AIs, discussing events related to their chemical structure, their specificity, and the effects of estrogen deprivation on target organs.
D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D047072:Aromatase Inhibitors; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced; D001943:Breast Neoplasms / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D004965:Estrogen Antagonists / Q000009:adverse effects*; D005260:Female; D005831:Genital Diseases, Female / Q000139:chemically induced; D006801:Humans; D018570:Risk Assessment; D013629:Tamoxifen / Q000009:adverse effects; D013927:Thrombosis / Q000139:chemically induced
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D013629:Tamoxifen