Five years of tamoxifen has long been considered the standard of care as adjuvant therapy for women with estrogen receptor–positive breast cancer. However, extending tamoxifen treatment for 10 years reduced the risk of dying by 29% during the second decade after diagnosis compared with standard therapy in the international Adjuvant Tamoxifen–Longer Against Shorter (ATLAS) study. ATLAS results were presented at the 2012 San Antonio Breast Cancer Symposium and published simultaneously in The Lancet.1,2
“Five years of tamoxifen is very effective, and we know there is a carryover effect after stopping, with about a 30% reduction in mortality over the next 5 years. ATLAS evaluated whether longer-term treatment could improve upon the carryover effect of 5 years of treatment,” said Richard Gray, MD, Clinical Trial Service Unit, University of Oxford, United Kingdom.
“In the period 10 to 14 years after diagnosis, we found many fewer recurrences: 617 in the group receiving 10 years of tamoxifen vs 711 in patients treated with 5 years of tamoxifen. Breast cancer mortality and overall survival were similarly affected by longer duration of tamoxifen,” he continued. There were 331 breast cancer–related deaths in the 10-year group vs 397 in the 5-year group, and 639 vs 722 deaths from all causes, respectively.
ATLAS enrolled 6,846 women with estrogen receptor–positive breast cancer from 36 countries between 1996 and 2005. About 50% had node-positive disease, and all women had been taking tamoxifen for 5 years. Women were randomly assigned to continue with 5 more years of tamoxifen or to no more tamoxifen.
The majority of women with ER-positive breast cancer were postmenopausal (89% in both groups, those continuing tamoxifen to 10 years and those stopping tamoxifen at 5 years). Approximately 9% and 10%, respectively, were premenopausal at ATLAS trial entry and 2% in each group were either perimenopausal or menopausal status unknown.
The effects of longer tamoxifen on rates of recurrence or death were larger after 10 years than in the period 5 to 9 years after diagnosis. Over the period 5 to 14 years after diagnosis, the risk of breast cancer death was 12.2% for 10-year users vs 15.0% for 5-year users, for an absolute gain of 2.8% favoring the longer treatment duration.
“The greatest benefit for longer-term tamoxifen emerged 10 to 14 years after diagnosis,” he said. In the second decade after diagnosis, those who took tamoxifen for 10 years had a 25% lower recurrence rate and 29% lower breast cancer mortality rate compared with those who had only 5 years of tamoxifen therapy.
The trade-off with 10 years vs 5 years of treatment could be more side effects, including an increase in endometrial cancer. But in this study, the cumulative risk of death from endometrial cancer between 5 and 14 years after diagnosis was 0.4% for the continuing tamoxifen users vs 0.2% for those who did not continue.
“The reduction in breast cancer deaths with 10 years of tamoxifen far outweighs this small risk of endometrial cancer and other adverse events, particularly in younger women who have a low background risk,” Prof. Gray said. “The absolute mortality gain with 10 years of tamoxifen at 15 years after diagnosis is 12%, or 1 in 8 balanced against 1 in 250 cases of endometrial cancer deaths,” he noted. ■
Disclosure: Prof. Gray reported no potential conflicts of interest.
1. Davies C, Pan H, Godwin J, et al, for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group: ATLAS—10 v 5 years of adjuvant tamoxifen in ER+ disease: Effects on outcome in the first and in the second decade after diagnosis. 2012 San Antonio Breast Cancer Symposium. Abstract S1-2. Presented December 5, 2012.
2. Davies C, Pan H, Godwin J, et al, for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. December 5, 2012 (early release online).