To switch or not to switch: should the updated Intergroup Exemestane Study alter our decision?
Adjuvant therapy for breast cancer with aromatase inhibitors improves survival compared with tamoxifen; however, whether they should be given upfront or sequentially after 2-3 years of tamoxifen in estrogen receptor-positive early breast cancer affecting postmenopausal women is unclear. The Intergroup Exemestane Study looked at 4724 postmenopausal patients with estrogen receptor-positive or unknown breast cancer who had been disease free for 2-3 years on tamoxifen and were randomly assigned to switch to exemestane or to continue tamoxifen for the remainder of a 5-year endocrine treatment period. A significant disease-free survival advantage (p = 0.0001) was seen in favor of exemestane, with an absolute benefit of 3.3% by the end of treatment. This trial is the first to show an overall survival advantage for switching in estrogen receptor-positive breast cancer (p<or= 0.05). In total, 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group, with a hazard ratio of 0.8 (95% confidence interval: 0.71-1.02; p = 0.08). A retrospective exclusion of patients who had estrogen receptor-negative disease improved the adjusted hazard ratio to 0.85 (0.69-1.0; p = 0.05). Contralateral breast cancer was reduced by 50% both in intention-to-treat and estrogen receptor-positive groups. These results indicate that a similar overall reduction in recurrence can be achieved with a switching or an upfront aromatase inhibitor strategy, but with a reduction in the overall morbidity. The 5% of early breast cancer patients who relapse in the first 2 years of tamoxifen treatment can be identified from 10% of the overall population. The remaining 90% could switch after 2-3 years. Controversy remains regarding whether switching is the optimal strategy and will only be resolved following the results of the Breast International Group 1-98 trial involving sequential therapy. Switching to exemestane for patients who have already had tamoxifen therapy for 2-3 years would appear to be an appropriate strategy for the majority of early breast cancer patients.
Iddon
Julie
J
University Hospital of South Manchester NHS Foundation Trust, Education & Research Centre, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK. julie.iddon@elht.nhs.uk
Bundred
Nigel J
NJ
D000730:Androstadienes / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*
D000730:Androstadienes; D047072:Aromatase Inhibitors; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C056516:exemestane