CHICAGO—Women diagnosed with estrogen-receptor (ER)-positive breast cancer who took tamoxifen for 10 years as adjuvant therapy had lower risk of late recurrence and lower risk of death compared to those who took the drug for 5 years. These results corroborate the findings of the international ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) trial published in December of last year. These new findings from the aTTom study (Adjuvant Tamoxifen: To Offer More?) conducted in Britain were presented at the American Society of Clinical Oncology (ASCO) annual meeting June 2.
“The results of aTTom and ATLAS are similar and reinforce each other,” said Richard G. Gray, MA, MSc, professor of medical statistics at the University of Oxford, Oxford, United Kingdom, and lead author of the aTTom trial, told Cancer Network. Gray was also involved in the ATLAS trial. “Together, the studies provide proof beyond reasonable doubt that continuing tamoxifen beyond 5 years reduces recurrence and death from breast cancer over the following years, with little effect in years 5 to 9 of treatment—most of the benefit [is] after year 10 of treatment.”
The combined data of the aTTom and ATLAS trials showed an additional 25% reduction in breast cancer mortality 10 years and beyond compared to 5 years of treatment (P = .0004).
Tamoxifen for 10 years can reduce death from breast cancer by one-third in the first decade and by one-half after the first decade compared with no tamoxifen over the 10-year period, according to the aTTom trial results.
Both of these studies are relevant for premenopausal women for whom 5 years of tamoxifen is the current standard for ER-positive breast cancer. The treatment is typically started after initial surgery or chemotherapy treatment. The 5-year treatment was previously established to reduce breast cancer mortality by almost 33% compared to no treatment over a 15-year period after diagnosis. The ATLAS trial, which enrolled 6,846 women internationally, showed that 10 years of tamoxifen therapy can decrease the mortality from cancer by one-half with the greatest benefit seen 10 to 14 years after the initial breast cancer diagnosis.
The aTTom trial enrolled 6,953 women in the United Kingdom between 1991 and 2005 who had already been taking tamoxifen for 5 years. The women were randomized to either continue tamoxifen for another 5 years or to stop the drug. Assessment of compliance, cancer recurrence, and death occurred annually throughout the study. The compliance rate was relatively high, 75% in the 10-year tamoxifen study arm. The breast cancer recurrence rate was 16.7% in the 10-year study group compared to 19.3% in the 5-year study group.
A total of 5,000 women were followed for over 10 years with some patients followed for 20 years. The treatment allocation had little effect on either recurrence rates or death rates during the period 5 to 9 years after diagnosis. After that, however (ie, during the second decade after diagnosis), the women who had been allocated to continue tamoxifen treatment had a 25% lower recurrence rate and a 23% lower breast cancer mortality rate than the women who had been allocated to stop after only 5 years.
According to Gray, no particular patient or tumor characteristic, other than ER-positive status influenced the reduction in recurrence in the 10-year tamoxifen study arm.
The most serious side effects of long-term tamoxifen were an increase in endometrial cancer risk: 102 women in the 10-year arm were diagnosed with endometrial cancer compared with 45 women in the 5-year arm, and 37 and 20 women died of their endometrial cancer, respectively. While these results were statistically significant, “10 years of tamoxifen prevents 30 times as many breast cancer deaths as it causes endometrial cancer deaths,” said Gray. “The benefits greatly outweigh the risks.”
The question now is whether clinicians will recommend 10 years of therapy and whether women will opt for longer therapy. Lisa Carey, medical oncologist and breast cancer specialist at the Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina told Cancer Network that these questions began after the ATLAS publication late last year. Carey says that she will recommend the longer regimen to patients at high risk of recurrence. “I think that low-risk tumors are less likely to benefit from the 10-year treatment.”
Tracey O'Connor, MD, associate professor and a breast cancer researcher at Roswell Park Cancer Institute, says she has already been offering 10 years of treatment to higher-risk premenopausal patients since the results of the ATLAS study, and that the side effect profile described in the aTTom study makes her even more comfortable with the recommendation. “I think the fact that the aTTom study confirms the results of ATLAS will make many more comfortable with this option.”
Whether women will opt for the extra 5 years of therapy will depend on their risk of recurrence and their personal value system, according to Carey, who suspects women who experience tamoxifen side effects are less likely to opt for the longer regimen.
O'Connor agrees. “While many patients will benefit from extended tamoxifen, those with very low-risk tumors may decide not to continue beyond 5 years.” O’Connor said higher-risk breast cancer patients will likely find these results compelling and will opt to continue tamoxifen for another 5 years.
Whether cost and access to tamoxifen for an additional 5 years will be an issue remains to be seen. Some health care providers were not willing to pay for longer tamoxifen, pending results from aTTom, said Gray.
While the ATLAS and aTTom studies addressed duration of tamoxifen therapy in premenopausal women, whether 10 years of tamoxifen is better for postmenopausal women is not clear. In these patients, a 5-year treatment with aromatase inhibitors has been shown to be superior to 5 years of tamoxifen, said Carey.
Even though some women in the two trials were followed for 20 years, Gray notes that longer-term follow-up of the patients on both these trials is still warranted.