American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors as Adjuvant Therapy for Women with Hormone Receptor Positive Breast Cancer: Status Report 2002 by Eric P. Winer, Clifford Hudis, Harold J. Burstein, Rowan T. Chlebowski, James N. Ingle, Stephen B. Edge, Eleftherios P. Mamounas, Julie Gralow, Lori J. Goldstein, Kathleen I. Pritchard, Susan Braun, Melody A. Cobleigh, Amy S. Langer, Judy Perotti, Trevor J. Powles, Timothy J. Whelan and George P. Browman Objective: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. Potential Interventions: Anastrozole, Letrozole and Exemestane. Outcomes: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. Evidence: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The ASCO prescribed Technology Assessment procedure was followed. Benefits/Harms: The ASCO Panel recognizes that a woman and her physician’s decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non–cancer-related risks and benefits. Conclusions: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the ATAC trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A five-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the Panel may be found summarized in Appendix 3) Validation: The conclusions of the Panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors. Sponsor: American Society of Clinical Oncology. == APPENDIX 3. Summary of the Panels’ Deliberations 1. What are the overall clinical implications of the findings from the ATAC trial for the adjuvant treatment of postmenopausal women with operable breast cancer? The panel is of the unanimous opinion that the results of the ATAC trial should be considered preliminary and that a five-year course of tamoxifen remains the standard adjuvant hormonal treatment for women with hormone receptor-positive breast cancer. The panel looks forward to updated data from the ATAC trial and other trials addressing questions about the third-generation aromatase inhibitors in the adjuvant setting. The panel encourages appropriate patients to consider participation in ongoing randomized trials. 2. Are all aromatase inhibitors equivalent? At the present time, the only available data using the third-generation aromatase inhibitors in the adjuvant setting are with anastrozole. The three commercially-available agents appear to be generally comparable in the metastatic setting. While extrapolation from the ATAC trial to the use of other aromatase inhibitors is reasonable, direct data are lacking. Based on the extensive body of clinical trial data from the advanced disease setting, the effects of the three available aromatase inhibitors would be expected to be similar. At this time, however, the only evidence in the adjuvant setting involves anastrozole. Furthermore, the panel notes that closely related agents with similar mechanisms of action may have different toxicity profiles. For this reason, the panel considers anastrozole the preferred agent if an aromatase inhibitor is used in the adjuvant setting. 3. What is the role of aromatase inhibitors in women who have already started taking tamoxifen in the adjuvant setting? There are currently no data to support substituting an aromatase inhibitor for tamoxifen as adjuvant therapy in a woman who has already started a course of tamoxifen. Outside of a clinical trial, women who are taking adjuvant tamoxifen and have not experienced significant side effects should continue tamoxifen therapy for a total of five years. Women experiencing intolerable side effects or who have developed a complication attributable to tamoxifen (i.e. thromboembolic event, persistent vaginal bleeding) may consider switching to an aromatase inhibitor, though the benefit of such a strategy is unproven and the optimal duration of such therapy is not known. 4. Is there a role for an aromatase inhibitor in women who have completed a five-year course of tamoxifen and are disease-free? Patients who have completed a five-year course of tamoxifen and are free of disease should not receive an aromatase inhibitor unless such therapy is part of a clinical trial. 5. If an aromatase inhibitor is used in the adjuvant setting, for how long should it be administered? Patients initiating aromatase inhibitor therapy in the adjuvant setting should be treated for at least two-to-three years based on the present experience from the ATAC trial. At this time, neither the efficacy nor the toxicity of a longer duration of therapy has been established. Clinicians and patients should expect to review the question of aromatase inhibitor duration as more data become available over the next several years. 6. What is the role of aromatase inhibitors in women who are premenopausal at the time of initiation of adjuvant hormonal therapy? Aromatase inhibitors are contraindicated in premenopausal women with functioning ovaries. Such therapy has not been evaluated and is likely to be ineffective. The use of LHRH agonists plus an aromatase inhibitor or oophorectomy plus an aromatase inhibitor in the adjuvant setting has not been studied and is not recommended outside of a clinical trial. 7. What is the role of aromatase inhibitors in women who are premenopausal at diagnosis and who experience interruption of ovarian function from chemotherapy? The panel cautions against the use of adjuvant aromatase inhibitors in women who are premenopausal at the time of diagnosis and have experienced a disruption in ovarian function. The panel has particular concerns about the use of aromatase inhibitors in women who have a substantial probability of resuming ovarian function. 8. What is the role of aromatase inhibitors in patients with ductal carcinoma in situ? Women with DCIS should not receive an aromatase inhibitor outside of the context of a clinical trial. 9. What is the role of aromatase inhibitors in women wishing to lower their risk of developing breast cancer? Women with an increased risk of developing breast cancer should not receive an aromatase inhibitor to decrease risk outside of a clinical trial. 10. What is the role of aromatase inhibitors in women whose tumors have negative hormone receptors? Women whose tumors are known to be hormone receptor-negative should not receive an aromatase inhibitor as adjuvant therapy. 11. What is the role of aromatase inhibitors in patients with certain biologic features, such as HER-2/neu positivity? The panel recommends against the use of HER-2 status in making decisions about adjuvant hormonal therapy. The clinical data to support the use of HER-2 status in this setting are inadequate. 12. What is the role of aromatase inhibitors in patients with a relative or absolute contraindication to the initiation of adjuvant tamoxifen? The panel considers it reasonable to initiate adjuvant hormonal therapy with an aromatase inhibitor in postmenopausal women who are thought to have a relative or absolute contraindication to adjuvant tamoxifen. Physicians and patients should carefully consider the significance of any relative contraindication in light of the proven benefits of adjuvant tamoxifen. 13. What is the role of aromatase inhibitors in patients who have developed hormone receptor-positive invasive breast cancer while taking either tamoxifen or raloxifene? While recognizing the paucity of direct data, the panel considers it reasonable to use adjuvant hormonal treatment with an aromatase inhibitor in postmenopausal women with hormone receptor-positive cancers who had been taking tamoxifen or raloxifene at diagnosis and who are, therefore, considered clinically resistant to these anti-estrogen agents. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.