Continued from Page 11 News on Aromatase Inhibitors researchers suggest that patients at high risk for relapse should be started on letrozole alone after surgery and initial treatment, but can switch to tamoxifen after two years if necessary. The TEAM Trial: Exemestane vs Tamoxifen Dr. Steve Jones presented the results of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial, a large study that included almost 10,000 women. The TEAM trial was originally planned to directly compare five years of tamoxifen with five years of exemestane among postmenopausal women who had hormone-receptor-positive early stage breast cancers. When the results of another study, the Intergroup Exemestane Study, found that patients who switched from tamoxifen to exemestane lived longer, the study design was changed so that all women who were initially given tamoxifen were switched to exemestane after two-and-a-half to three years for a total of five years of treatment. In order to study the effects of treatment with only exemestane, Dr. Jones presented the analysis of patients who were treated for the initial 2.75 years before the switch from tamoxifen to exemestane was allowed. The initial analysis showed that exemestane was not significantly better than tamoxifen; patients did not appear to live longer without a relapse of breast cancer or overall. But the investigators were able to see some reasons for this negative result. The trial was designed as an open-label study, which means that all patients know which drug they are getting. As a result, almost 30 percent of patients selected for tamoxifen switched to exemestane even before the trial was changed to allow this switch. About 20 percent of patients also switched from exemestane to tamoxifen. Once the researchers removed the results from all patients who had either never been treated or switched treatments early, they were able to see that women who were treated with exemestane had better results; the length of time after treatment that patients lived without any sign of breast cancer (referred to as disease-free survival) Aromatase inhibitor alone vs. tamoxifen alone (Group 1) Aromatase inhibitor after 2-3 years of tamoxifen vs. tamoxifen alone (Group 2) 12 Spring 2009 Volume 118 Location of Breast Cancer Relapse Same breast Opposite breast News From SABCS 2008 was much higher with exemestane than with tamoxifen. Similarly, the time to relapse and the time before the development of metastases in the bone, breast or lung were also greater with exemestane than tamoxifen. Dr. Jones suggested that these results may indicate that patients live longer overall after treatment with exemestane than tamoxifen. Meta-analyses of Aromatase Inhibitor Trials Meta-analyses are statistical analyses which combine information from many different trials that address the same hypothesis (educated guess). Investigators of the Aromatase Inhibitor Overview Group pooled the results from almost 20,000 women who had participated in five separate trials that compared aromatase inhibitors to tamoxifen.Two of these trials had compared five years of an aromatase inhibitor and five years of tamoxifen (Group 1). The other three trials had compared a switching strategy (tamoxifen for two or three years followed by an aromatase inhibitor) to tamoxifen alone (Group 2). The results of the meta-analysis showed that the risk of a relapse of breast cancer was 23 percent lower with aromatase inhibitors alone than tamoxifen alone (Group 1). Similarly, the risk of relapse was 29 percent lower with patients who had been switched from tamoxifen to aromatase inhibitors than for patients who had continued tamoxifen (Group 2). In both groups, women lived longer overall with aromatase inhibitors than tamoxifen, although in group 1, the better overall survival could have resulted from chance. Please see the section on risk reduction on Page 8 for an explanation on relative risk and absolute risk. The benefit of aromatase inhibitors was different depending on where the cancer relapsed (see table below). Overall, the meta-analysis showed that aromatase inhibitors alone or as a switch treatment after two to three years of tamoxifen following surgery better prevented relapses of breast cancer when compared with tamoxifen. Other parts of the body (distant recurrence) Same breast Opposite breast Other parts of the body (distant recurrence) Relative Risk Reduction With Aromatase Inhibitor vs. Tamoxifen 30 percent 41 percent 16 percent to 18 percent 40 percent 35 percent 23 percent to 24 percent
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