Aromatase Inhibitors (AIs) Versus Not (Placebo/Observation) as Late Extended Adjuvant Therapy for Postmenopausal Women with Early Stage Breast Cancer (BC): Overviews of Randomized Trials of AIs after ∼ 5 Years of Tamoxifen.

Abstract

Abstract Backround: 5 yrs of adjuvant tamoxifen (Tam) substantially reduces recurrence and mortality in ER+ breast cancer. Two to five years of late extended AI (anastrozole, exemestane or letrozole) adjuvant therapy after ∼ 5 years of Tam has been studied in prospective trials in postmenopausal patients (pts) in comparison with placebo or observation.Methods: A meta-analysis of outcomes data submitted to EBCTCG was conducted for four clinical trial data sets: NCIC CTG MA17; NSABP B33; ABCSG VIA; ATENA. The primary analysis involved patients with tumors reported to be ER positive with endpoints of first BC recurrence (all, local only, contralateral BC only, distant), death with and without recurrence, any death. All p-values were 2-sided. Follow-up for MA.17 was censored at the date of un-blinding; this was not possible with B-33, which consequently includes some events following subsequent treatment crossovers.Results: Preliminary results are available; updated and sub-group analyses including progesterone receptor, age, grade and nodal status will be presented. Highlights include: at a median follow-up of 2.5 years, AI therapy was associated with an absolute 2.9% [standard error (SE) 0.5] decrease in BC recurrence [relative decrease, 43% (SE 8), p<0.00001] and an absolute 0.5% (SE 0.3) decrease in BC mortality [relative decrease 27% (SE 17), 2p=0.11].Conclusions: A meta-analysis of 4 clinical trials, two of which were stopped early showed that ∼2-5 years late extended adjuvant therapy beyond 5 years from diagnosis produced a highly significant reduction in BC recurrence compared with no therapy. A trend toward improved survival is also seen. The magnitude of the effect seen on disease free and overall survival in these analyses is likely under estimated because of some cross-over after un-blinding. Longer than five years of adjuvant endocrine therapy is superior to just 5 years in ER+ breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4081.