August 2013, Vol 2, No 5
Ten Years of Tamoxifen Is Superior to 5 Years in ER+ Breast CancerUncategorized
Ten years of adjuvant tamoxifen is superior to 5 years in reducing the rates of late recurrence and death in women with estrogen receptor (ER)-
positive breast cancer, reported Richard G. Gray, MSc.
Previously, 5 years of tamoxifen have been shown to reduce breast cancer mortality by about one-third over 15 years. Gray presented data from a study known as aTTom (Adjuvant Tamoxifen: To Offer More?), which demonstrated an additional 25% reduction in cancer recurrence and death rates from year 10 onward in women treated for 10 years compared with 5 years of tamoxifen.
The aTTom results complement and confirm those from a recently published study called ATLAS (Adjuvant Tamoxifen: Longer Against Shorter; Lancet. 2013;381:805-816).
In aTTom, 6953 women in the United Kingdom who had been taking tamoxifen for 5 years were randomized to continuing treatment for an additional 5 years or stopping treatment. About 75% of the women assigned to continue tamoxifen had continued taking it for the 5 extra years.
Ten years of tamoxifen reduced breast cancer recurrence by 15% compared with 5 years (P=.003). The rate of breast cancer deaths was reduced by 12% with 10 years relative to 5 years (P=.06). “Treatment allocation had little effect on either recurrence rates or death rates from 5 to 9 years after diagnosis, but the benefit of longer treatment became evident in the second decade after diagnosis,” said Gray, professor of medical statistics at the University of Oxford, United Kingdom. The relative reduction in the risk of death with assignment to 10 years of tamoxifen increased to 21% in years 10 to 14 after diagnosis, and to 25% in year 15 of follow-up and later.
There were no significant differences in the rates of death without recurrence or all-cause mortality between the 2 groups, although a significant difference in overall survival in favor of 10 years of tamoxifen emerged from year 10 onward (P=.016).
Extending the use of tamoxifen approximately doubled the risk of endometrial cancer (from 1.3% to 2.9%) and endometrial cancer death (from 0.6% to 1.1%), but the net clinical benefit favored 10 years of treatment, he said.
Compared with not taking tamoxifen, 10 years of tamoxifen reduces the breast cancer death rate by one-third in the first 10 years after diagnosis and by half subsequently, said Gray. The benefit of tamoxifen in the aTTom study may be even greater than reported because 60% of the enrolled patients had an unknown ER status. An estimated 15% of patients likely had ER- negative disease and did not benefit from tamoxifen.
The findings from aTTom complement and confirm those from ATLAS. The combined data of aTTom and ATLAS, with more than 17,000 patients, show a significant 15% reduction in breast cancer mortality overall (P=.001) and an additional 25% reduction in breast cancer mortality 10 years and beyond with 10 years of tamoxifen compared with 5 years of treatment (P=.00004).
Together, the results of the aTTom and ATLAS trials constitute “proof beyond reasonable doubt” that continuing tamoxifen beyond 5 years reduces the risk of late recurrence and reduces breast cancer mortality, said Gray.
Late relapses remain a concern in ER-positive breast cancer, even with the introduction of effective early therapies, said Ann H. Partridge, MD, MPH, medical oncologist, Dana-Farber Cancer Institute, Boston, MA, and extended tamoxifen therapy appears to reduce the risk of late relapses. In aTTom and ATLAS, extending tamoxifen primarily reduced the risk of recurrences starting after year 7.
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