The Evolving Role of Aromatase Inhibitors in the Adjuvant Breast Cancer Setting
Tóm tắt
Third-generation aromatase inhibitors (AIs) have shown at least equivalent or superior efficacy to tamoxifen in the first-line treatment of women with hormone-dependent metastatic breast cancer. Similar results have been obtained in the neoadjuvant setting. These studies suggested that AIs may also have significant efficacy in the adjuvant setting, and evaluation against tamoxifen is ongoing. Unlike tamoxifen, which interferes with estrogen receptor-dependent gene expression, AIs prevent the formation of estrogen. Therefore, they do not have the mixed agonistic/antagonistic properties inherent in tamoxifen that cause the adverse events (thromboembolism, endometrial cancer) associated with this agent. In contrast, estrogen depletion may adversely affect bone density and lipid profile. The evaluation of AIs in the adjuvant setting is ongoing in eight major clinical trials. Many of these trials also have subprotocols designed to assess the safety of these agents. Although it will take many years to assess the full impact of adjuvant therapy with AIs, early results from the ATAC (Arimidex and Tamoxifen Alone or in Combination) trial with anastrozole have been reported, and a significant advantage in disease-free survival and the occurrence of contralateral breast cancer noted with the AI compared with tamoxifen. Early results with letrozole from the (J)MA-17 and BIG 1–98 trial (the International Breast Cancer Study Group trial) are expected to follow shortly. It is expected that the ongoing adjuvant trials will provide valuable information concerning efficacy, adverse-effect profile of long-term therapy, resistance to endocrine therapy and the usefulness of sequential treatment with multiple agents. A number of important questions will remain to be answered, however, including the length of time an AI should be administered after surgery and whether any one of the AIs would show superiority over the others in head-to-head comparison.
Tài liệu tham khảo
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