Continuing Tamoxifen to 10 Years Produces Further Reductions in Breast Cancer Recurrence, Death
CHICAGO—Results from the aTTom and ATLAS trials together provide “proof beyond reasonable doubt” that continuing adjuvant tamoxifen beyond 5 years in estrogen receptor–positive (ER+) disease reduces breast cancer recurrence, with benefit occurring primarily after year 7, a plenary presentation concluded at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
“Continuing tamoxifen beyond 5 years also reduces breast cancer mortality,” said Richard G. Gray, MA, MSc, of the University of Oxford, Oxford, United Kingdom. The aTTom trial, with its international counterpart, ATLAS, found 10 years of tamoxifen compared with no tamoxifen reduced breast cancer mortality by one-third in the first decade and by half in the second decade.
Sylvia Adams, MD, ASCO spokesperson and breast cancer expert, called these results “practice changing for premenopausal women with hormone receptor–positive breast cancer and especially relevant for women who are at high risk of recurrence.” The ATLAS findings were recently published in The Lancet.
The objectives of aTTom and ATLAS were to randomly assign at least 20,000 women between 5 and 10 years of tamoxifen to detect reliably, or refute reliably, a 2% to 3% improvement in survival.
To determine how 10 years of tamoxifen compared with 5 years, between 1991 and 2005 the investigators in 176 UK centers randomly assigned 6,953 women who had been taking tamoxifen for 5 years to continue treatment with tamoxifen to year 10 or to stop immediately. Of the women, 2,755 were ER+ and 4,198 had not been tested for ER; 80% were estimated to have been ER+ if their status had been known.
The women were then contacted annually to assess treatment compliance, recurrence, hospital admissions, and mortality. Approximately 75% of women in the 10-year group continued to take tamoxifen. Approximately 5,000 women were followed for more than 10 years after randomization, some for as long as 20 years.
Allocation to continue tamoxifen reduced breast cancer recurrence; 580 women in the group that continued versus 672 in the group that stopped had disease recurrence (rate ratio [RR], 0.85; 95% CI: 0.76-0.95; P=0.003), or 32% recurrence in the group that stopped versus 28% in the group that continued. Gray said this reduction was time dependent, with a rate ratio for continue:stop of 1.10 during years 5 to 6, 0.79 during years 7 to 9, and 0.78 for years 10 to 14; for years 15+, it was 0.66. For all years, the odds ratio was 0.85.
Longer treatment also reduced breast cancer mortality. In the group that continued, there were 404 deaths (11.6%) compared with 452 deaths (13.0%) in the group that stopped (RR, 0.88; 95% CI: 0.77-1.01; P=0.06), for a 21% versus 24% mortality rate, respectively. Odds ratio was 1.17 for years 5 to 6; 0.99 for years 7 to 9; 0.79 for years 10 to 14; and 0.75 for years 15+.
At 10 years, there were 102 endometrial cancers compared with 45 at 5 years (RR, 2.20; 95% CI: 1.31-2.34; P<0.0001) with 37 (1.1%) versus 20 (0.6%) deaths (absolute hazard 0.5%, P=0.02).
Researchers are planning to follow women in this and the ATLAS study for at least 5 more years to see if there is additional long-term benefit. A retrospective analysis of combined data from aTTom, ATLAS, and three smaller trials will be conducted to determine if there are subgroups of women that benefit the most from longer tamoxifen treatment. Ongoing clinical trials are comparing 5-year and 10-year use of aromatase inhibitors to see if longer use leads to more benefit, as has been seen with tamoxifen.
This research was supported by Cancer Research UK and the UK Medical Research Council.