aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer.

5 Background: In estrogen-receptor-positive (ER+) early breast cancer, 5 years of tamoxifen reduces breast cancer death rates by about a third throughout years 0-14. It has been uncertain how 10 years of tamoxifen compares with this. Methods: During 1991-2005, 6,953 women with ER+ (n=2755), or ER untested (4198, estimated 80% ER+ if status known) invasive breast cancer from 176 UK centres were, after 5 years of tamoxifen, randomized to stop tamoxifen or continue to year 10. Annual follow-up recorded compliance, recurrence, mortality, and hospital admissions. Results: Allocation to continue tamoxifen reduced breast cancer recurrence (580/3468 vs 672/3485, p=0.003). This reduction was time dependent: rate ratio 0.99 during years 5-6 [95%CI 0.86-1.15], 0.84 [0.73-0.95] during years 7-9, and 0.75 [0.66-0.86] later. Longer treatment also reduced breast cancer mortality (392 vs 443 deaths after recurrence, p=0.05), rate ratio 1.03 [0.84-1.27] during years 5-9 and 0.77 [0.64-0.92] later; and overall mortality (849 vs 910 deaths, p=0.1), rate ratio 1.05 [0.90-1.22] during years 5-9 and 0.86 [0.75-0.97] later. Non-breast-cancer mortality was little affected (457 vs 467 deaths, rate ratio 0.94 [0.82-1.07]). There were 102 vs 45 endometrial cancers RR=2.20 (1.31-2.34, p<0.0001) with 37 (1.1%) vs 20 (0.6%) deaths (absolute hazard 0.5%, p=0.02). Combining the similar results of aTTom and its international counterpart ATLAS (Lancet 2013) enhances statistical significance of recurrence (p<0.0001), breast cancer mortality (p=0.002) and overall survival (p=0.005) benefits. Conclusions: aTTom confirms that, in ER+ disease, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence, from year 7 onward, and breast cancer mortality after year 10. Taken together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen vs none, these results indicate that 10 years of adjuvant tamoxifen, compared to no tamoxifen, reduces breast cancer mortality by about one third in the first 10 years following diagnosis and by a half subsequently. Clinical trial information: ISRCTN17222211.