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Extended tamoxifen reduced breast cancer recurrence, mortality
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CHICAGO — Women with ER-positive breast cancer who underwent 10 years of adjuvant treatment with tamoxifen were at reduced risk for late recurrence and breast cancer-related mortality compared with those who underwent 5 years of treatment, according to results of the phase 3 aTTom study presented at the ASCO Annual Meeting.
The longer duration of tamoxifen treatment was associated with increased adverse effects, but the overall benefits outweigh any potential risks of extended therapy, researchers said.
“Tamoxifen is a very effective treatment,” Richard G. Gray, MA, MSc, professor of medical statistics at the University of Oxford in the United Kingdom, said during a press conference. “In trials of these patients not treated with tamoxifen, about 50% have disease recurrence within 15 years. If patients took tamoxifen, this number reduced to 33%. However, even if a patient is on tamoxifen for 5 years, there is a very high risk for the cancer recurring within the next 5 years.”
The aTTom study showed extended tamoxifen reduced breast cancer recurrence by 25% and mortality by 23%.
The results confirm and complement the findings of the international ATLAS study, which were presented at the San Antonio Breast Cancer Symposium in 2012 and published in The Lancet earlier this year. When data from both trials were combined, the statistical significance of recurrence (P<.0001), mortality (P=.002) and OS (P=.005) were increased, according to information provided by the researchers.
Until recently, there were doubts about whether continuing tamoxifen beyond 5 years was worthwhile, Gray said.
To compare the efficacy of extended treatment with the standard regimen, Gray and colleagues enrolled 6,953 women between 1991 and 2005. All patients had undergone 5 years of tamoxifen treatment.
Researchers randomly assigned 3,468 women to an additional 5 years of tamoxifen, while the other 3,485 were assigned to discontinue treatment.
Treatment compliance was 75% in the 10-year group. Researchers followed 5,000 women for more than 10 years after randomization, and some were followed as long as 20 years.
The rate of breast cancer recurrence was 16.7% in the extended treatment arm compared with 19.3% among women who discontinued treatment after 5 years. The decrease in recurrence was time-dependent among women assigned to 10-years of treatment. The rate ratio was 0.99 between years 5 and 6 (95% CI, 0.86-1.15), 0.84 between years 7 and 9 (95% CI, 0.73-0.95) and 0.75 thereafter (95% CI, 0.66-0.86).
Mortality from breast cancer also decreased with longer treatment. The rate ratio between years 5 and 9 was 1.03 (95% CI, 0.84-1.27) and 0.77 thereafter (95% CI, 0.64-0.92). The rate ratio for overall mortality was 1.05 between years 5 and 9 (95% CI, 0.90-1.22) and 0.86 thereafter (95% CI, 0.75-0.97).
After year 9 of treatment, researchers observed a 25% decrease in breast cancer recurrence and a 23% decrease in mortality when compared with women who discontinued treatment after 5 years.
Side effects of tamoxifen treatment are similar to menopausal symptoms, such as hot flashes and night sweats. Rare but serious adverse effects can include increased risk of endometrial cancer and stroke.
Endometrial cancer risk was higher in the extended tamoxifen arm; however, because endometrial cancer often is detected early, the researchers estimated 30 deaths from breast cancer would be prevented for every 1 endometrial cancer death.
There was no excess incidence of stroke in the 10-year tamoxifen arm, according to Gray and colleagues.
Researchers intend to follow women in the aTTom and ATLAS studies for at least another 5 years to determine if there are additional long-term benefits. A retrospective analysis of the two studies, as well as three smaller trials, will be conducted to evaluate whether extended tamoxifen treatment offers particular benefits to certain subgroups of women.
For more information:
Gray RG. Abstract #5. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: The research was supported by Cancer Research UK and the UK Medical Research Council.
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Sylvia Adams, MD
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 [they are] especially relevant for women who are at high risk of recurrence.
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Clifford A. Hudis, MD
This abstract is really important from both a science point of view and a global health point of view. The results of the ATLAS trial — presented at the San Antonio Breast Cancer Symposium at the end of 2012 — were seen by many as practice changing. But the best science is science that can be replicated independently. The aTTom trial does just that. The results are quite similar to what was seen with ATLAS, but this is really important because it means that, globally, where there is likely to be access to an inexpensive and safe drug like tamoxifen, we now know very reliably that 10 years of therapy is superior to 5 years of therapy in the postoperative, adjuvant setting when the estrogen receptor or progestin receptor is present in invasive breast cancer. This is a big deal because it’s maybe the last chapter — or near the last chapter — in the development of the adjuvant use of tamoxifen, and it has immediate repercussions around the world.
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Back to TopJyoti D. Patel, MD, FACP
This study provides conclusive evidence that the longer-duration tamoxifen lowered the risk for recurrent disease. This is relevant to the hundreds of thousands of women around the world who do take tamoxifen. The longer duration has a considerable impact with a drug that is inexpensive.
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Debasish “Debu” Tripathy, MD
We know that women with hormone receptor-positive cancers can recur 5, 10 or even 15 years later. The idea of studying extended hormonal therapy beyond 5 years had been brought up 10 to 15 years ago. Two major trials were designed to compare 5 years vs. 10 years of tamoxifen. The ATLAS trial, the larger of the two, showed about 3% to 4% fewer deaths due to breast cancer with 10 years of therapy. The aTTom trial showed about 15% fewer recurrences and about a 2% reduction in death, which was of borderline statistical significance. The findings add to the evidence that longer hormonal therapy should be considered, especially for higher-risk patients.
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