Extending tamoxifen reduced risk for late breast cancer recurrence and improved survival
Ten years of adjuvant treatment with tamoxifen provided women with estrogen receptor (ER)-positive breast cancer greater protection against late recurrence and death from breast cancer compared with the current standard of 5 years of tamoxifen, according to the international ATLAS (Adjuvant Tamoxifen–Longer Against Shorter) study.
“Five years of adjuvant tamoxifen is already an excellent treatment that substantially reduces the 15-year risk for recurrence and death from estrogen receptor-positive breast cancer, but ATLAS now shows that 10 years of tamoxifen is even more effective,” said Christina Davies, MD, of the University of Oxford in the United Kingdom.
The researchers enrolled 6,846 women with ER-positive breast cancer between 1996 and 2005. Half had node-positive disease. All the women had been using tamoxifen for 5 years, and the researchers randomly assigned them to continue treatment for another 5 years or to stop immediately.
After 8 years of follow-up, the researchers observed 1,328 breast cancer recurrences and 728 deaths after recurrence. The treatment allocation had little effect on either recurrence rates or death rates during the period 5 to 9 years after diagnosis. However, during the second decade following diagnosis, recurrence was 25% lower and mortality from breast cancer was 29% lower in the women who continued tamoxifen therapy compared with women who stopped therapy after 5 years.
“The main additional benefit from continuing tamoxifen treatment is to reduce breast cancer mortality during the second decade after diagnosis,” Davies said. “We already knew that 5 years of tamoxifen reduces breast cancer mortality in this late period by almost a third in comparison with no tamoxifen. We now know that 10 years of tamoxifen is even better, approximately halving breast cancer mortality during the second decade after diagnosis.”
Risk of death from breast cancer 5 to 14 years after diagnosis was 12.2% among those who continued use versus 15% among those who stopped, which was an absolute gain of 2.8%. The researchers observed the greatest benefit during the time period 10 to 14 years after diagnosis.
Davies noted that continuing tamoxifen use can increase side effects, with endometrial cancer being the most life-threatening. Because endometrial cancer is generally curable, the cumulative risk for death between 5 and 14 years after diagnosis was 0.4% versus 0.2%. Because this risk is heavily outweighed by the reduction in breast cancer deaths, overall mortality was significantly reduced by longer treatment. In premenopausal women, for whom tamoxifen is often the endocrine treatment of choice, there was no apparent excess of endometrial cancer.
Davies said, “ATLAS showed that protection against breast cancer recurrence and death is greater with 10 years than with 5 years of tamoxifen use. Women and their doctors should be aware of this evidence when deciding how long to continue tamoxifen, or any other endocrine treatment.”
This study was presented at the CTRC-AACR San Antonio Breast Cancer Symposium, held December 4-8, and also simultaneously published in The Lancet (2012; doi:10.1016/S0140-6736(12)61963-1).