ASCO 2013: 10 Years of Tamoxifen Better Than 5 in Reducing Breast Cancer Recurrence and Death
Ten years of adjuvant treatment with tamoxifen reduces breast cancer recurrence and mortality among women treated for early-stage estrogen receptor (ER)–positive breast cancer, according to results of the British phase III aTTom study. These findings, presented at the 2013 ASCO Annual Meeting (Abstract 5), complement and confirm the results of the recently published international ATLAS study.
“If there was doubt that ATLAS might have been too good to be true, this shows that it is true. There is absolutely no doubt that tamoxifen reduces mortality,” stated Richard G. Gray, MA, MSc, lead author of the aTTom study and Professor of Medical Statistics at the University of Oxford, United Kingdom.
“This landmark trial confirms recent findings of the ATLAS trial showing that extending therapy with tamoxifen to 10 years significantly lowers breast cancer recurrences and mortality. These results are therefore practice-changing for premenopausal women with hormone receptor–positive breast cancer and especially relevant for women who are at high risk of recurrence," said Sylvia Adams, MD, Associate Professor of Medicine, New York University School of Medicine.
Benefits Outweigh Risks
Prior studies have shown that 5 years of tamoxifen reduces breast cancer death rates by about one-third over a 15-year period following diagnosis. This study shows that, compared to 5 years of tamoxifen therapy, 10 years of tamoxifen reduces breast cancer recurrence and death rates by an additional 25% from year 10 onward. The researchers estimated that, compared to taking no tamoxifen, 10 years of tamoxifen reduces breast cancer death rate by one-third in the first 10 years after diagnosis and by half subsequently.
Although side effects are also increased with longer tamoxifen use, the researchers concluded that the overall benefits greatly outweigh the risk of continuing therapy.
Women taking tamoxifen can experience side effects similar to menopausal symptoms, such as night sweats and hot flashes. Rare but serious side effects of tamoxifen include increased risk of endometrial cancer, blood clots, and stroke. No excess incidence of stroke was observed with 10 years of tamoxifen therapy, though endometrial cancer risk was higher in this arm. Researchers estimated that for every endometrial cancer death that occurs as a side effect of long-term tamoxifen, there would be 30 deaths from breast cancer prevented.
Compliance Was Good
“Five years of adjuvant tamoxifen is already an excellent treatment, but we thought that longer treatment might be even better because women with ER-positive breast cancer can have recurrences long after treatment is completed. Until now, though, there have been doubts whether continuing tamoxifen beyond 5 years is worthwhile,” Professor Gray said. “This study and its international counterpart ATLAS confirm that there is definitely a survival benefit from longer tamoxifen treatment, and many doctors will likely recommend continuing tamoxifen for an extra 5 years.”
Between 1991 and 2005, 6,953 women (2,755 ER-positive and 4,198 ER-untested) in the United Kingdom who had been taking tamoxifen for 5 years were randomly assigned to continue treatment with tamoxifen for another 5 years or to stop immediately. The women were contacted yearly to assess treatment compliance, recurrence, hospital admissions, and death rates. Compliance was good, with about 75% of women in the 10-year group continuing to take tamoxifen.
Effects Greater in Second Decade
With 5,000 women followed for more than 10 years after randomization, and some as long as 20 years, fewer breast cancer recurrences occurred in the 10-year tamoxifen group than in the 5-year group (16.7% vs 19.3%). Longer treatment also reduced the risk of breast cancer mortality (392 vs 443 deaths after recurrence; P = .05). The effect was greater in the second decade after the diagnosis of breast cancer when women who had been allocated to continue tamoxifen treatment had a 2% lower recurrence rate and a 23% lower breast cancer mortality rate than the women who had been allocated to stop after 5 years.
Researchers are planning to follow women in this study 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.
This research was supported in part by Cancer Research UK and the UK Medical Research Council.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
