The Study: As a reminder, over 8K women were randomized to one of four post-operative endocrine therapy regimens:  letrozole x 5 years,  tamoxifen x 5 years,  letrozole x 2 years → tamoxifen x 3 years, or  tamoxifen x 2 years → letrozole x 3 years. Which all turned out to be a confusing way of comparing women who received letrozole first (arms  + ) to women who received tamoxifen first (arms  + ). We now have long term results with a median follow-up of over 12 years demonstrating a persistent benefit with letrozole in terms of disease-free survival (DFS) and overall survival, though they don’t remain "significant" due to dwindling numbers of persistent enrollees. Interestingly, contralateral breast cancer incidence in the first decade was 1.5x more common among women who received tamoxifen and in the second decade was 2x more common among women who received letrozole. Most important, patients in arm  had rates of DFS within a percentage point of those in arm  at all time points, suggesting transitioning to tamoxifen upon side effects such as joint pain should not forfeit cancer outcomes.
Bottom Line: There is a relative DFS benefit of roughly 9% with letrozole over tamoxifen that appears to last forever, translating to an absolute benefit of 3% (or <1% when transitioning to tamoxifen from letrozole). | Ruhstaller, J Clin Oncol 2018