The landmark aTTom study showed that 10 years of adjuvant tamoxifen is superior to 5 years of tamoxifen in reducing the risk of breast cancer recurrence or death but that the full survival benefits of extended treatment do not emerge until after the 10 years of treatment. These findings, which were presented at the ASCO Annual Meeting,1 mirror those of the companion study ATLAS, which was presented at the San Antonio Breast Cancer Symposium in December 2012.2
Proof Beyond Doubt
“ATLAS and aTTom between them provide proof beyond a reasonable doubt that continuing [adjuvant] tamoxifen beyond 5 years reduces recurrence over the long term, with the benefit [reduced recurrence] seen mainly after year 7. Extended tamoxifen also reduces the risk of breast cancer mortality, and this reduction is seen after year 10,” stated lead author Richard G. Gray, MSc, Professor of Medical Statistics, University of Oxford, United Kingdom.
Previous studies demonstrated that 5 years of tamoxifen reduced the breast cancer death rate by about 33% throughout 15 years of follow-up. The aTTom trial showed that 5 years more of tamoxifen therapy reduced tumor recurrence and breast cancer death rates by an additional 25% from year 10 onward compared with 5 years. Thus, the researchers estimate, compared to taking no tamoxifen, 10 years of tamoxifen reduces breast cancer death rate by a third in the first 10 years after diagnosis and by half subsequently.
Major Results
The study enrolled 6,953 women with early breast cancer who had taken adjuvant tamoxifen for 5 years. Participants were randomly assigned to receive 5 years of additional tamoxifen or to stop tamoxifen. The women were evaluated annually to assess tumor recurrence, rates of hospitalization and death, and compliance. About 75% of women in the 10-year tamoxifen group were adherent to treatment.
“An interim analysis of this trial in 2008 showed no significant benefit of extended tamoxifen in terms of tumor recurrence and breast cancer death. But follow-up was not long enough. Five years later, there is remarkable improvement with 10 years of tamoxifen,” Prof. Gray told listeners at the Plenary Session.
At 10 years of follow-up from randomization, extended tamoxifen significantly reduced the risk of tumor recurrence: 28% vs 32% for women stopping after 5 years of tamoxifen (P = .003). The mortality benefit of extended tamoxifen was also evident: 21% in the extended tamoxifen group vs 24% in the placebo group, for borderline significance (P = .06). “Taken together, ATLAS and aTTom show that there is definitely a survival benefit from longer tamoxifen treatment, with the curves diverging after 10 years,” he emphasized.
Tamoxifen Drawbacks
The downside of 10 years of tamoxifen is a doubling of the number of endometrial cancers, from 45 (1.3%) with 5 years to 102 (2.9%) with 10 years (P < .0001).
Also, more women on longer tamoxifen treatment died of endometrial cancer: 20 deaths after 5 years of tamoxifen and 37 deaths after 10 years (P = .02). Despite this, fewer deaths from all causes were observed with 10 years of treatment, he said. ■
Disclosure: Prof. Gray reported no potential conflicts of interest.
References
1. Gray RG, et al: aTTom: ASCO Annual Meeting. Abstract 5. Presented June 2, 2013.
2. Davies C, et al, for the ATLAS Collaborative Group: ATLAS—10 v 5 years of adjuvant tamoxifen in ER+ disease. 2012 San Antonio Breast Cancer Symposium. Abstract S1-2. Presented December 5, 2012.
