Optimal use of aromatase inhibitors for adjuvant treatment of hormone-sensitive early breast cancer: Up front or sequenced after tamoxifen?

Abstract

541 Background: The aromatase inhibitors (AIs) are more effective than tamoxifen when used for the adjuvant treatment of early breast cancer. However, it is still unclear whether it is better to start initially with an AI or use it after a 2–3-year period of tamoxifen treatment. No clinical trial data are likely to be available until 2008, although earlier modeling data have shown that an upfront strategy may be more favorable (Cuzick et al. Br J Cancer 2006: 27; 460–464). Here we update the model with all newly reported data. Methods: A model has been constructed to compare the use of an AI upfront with AI sequencing after varying periods of initial treatment with tamoxifen. Recurrence rates and time lost to recurrence for the first 10 years of follow-up are modeled for a range of efficacy parameters. Results: Results predicted from the model are presented in the table . For a 5-year carryover period, the predicted recurrence rate at 10 years is 17.7% for upfront use of an AI compared with 22.9% for 5 years of tamoxifen, leading to one less recurrence for every 19 women treated. The average time lost to recurrence is reduced by 2.8% or 3.4 months. With updated data, the model predicts an AI upfront strategy will dominate a sequencing strategy. However, the model also demonstrates that using 10 years of tamoxifen, or a sequence of 5 years of tamoxifen followed by 5 years of an AI, is superior to using 5 years of tamoxifen. This indicates that longer duration of treatment with an AI is likely to be beneficial, especially for younger women, and deserves further investigation. Conclusion: The current modeling data suggest that using an AI as upfront adjuvant treatment is better than using an AI in sequence after 2 or more years of tamoxifen. [Table: see text] No significant financial relationships to disclose.