In a study that many breast cancer experts say may change practice, researchers have reported that extending the use of the drug tamoxifen to 10 years -- rather than the currently recommended five years -- could save lives by thwarting cancer's return.
Breast cancer can recur even years after treatment. For the three quarters of breast cancers that are estrogen receptor (ER) positive, tamoxifen and other hormone therapy drugs have lowered the risk of cancer coming back.
Long awaited data on the breast cancer drug tamoxifen from a large clinical trial was released today at the San Antonio Breast Cancer Symposium and published in the medical journal The Lancet. The Adjuvant Tamoxifen: Longer Against Shorter, or ATLAS, trial began in 1996 and is one of the largest breast cancer trials of its type. It is a large multi-center study involving more than 12,000 women with early breast cancer.
Unlike earlier studies, which did not show a clear benefit of taking tamoxifen for longer than five years, this trial reports that lives are saved by taking tamoxifen for longer as time progresses.
"Five years of adjuvant tamoxifen is already an excellent treatment that substantially reduces the 15-year risk for recurrence and death," study author Dr. Christina Davies said in a statement. "We now know that 10 years of tamoxifen is even better, approximately halving breast cancer mortality during the second decade after diagnosis"
In the ATLAS study, 6,846 women with ER positive breast cancer, who had already completed five years of tamoxifen therapy, were randomized to either stop the drug or continue taking it for five more years. Recruitment began in 1996. Participants were followed yearly for breast cancer recurrence, death, and serious side effects.
Over the studied period, both breast cancer recurrences and deaths were lower among those who took tamoxifen for 10 years rather than just five years. Fifty-six fewer women were observed to die of breast cancer during follow-up among the group who continued tamoxifen than among the group who stopped. This was a 2.8 percent reduction in breast cancer mortality during the 10 years of the trial.
However, experts say more tamoxifen could have consequences, including a higher risk of uterine cancer and blood clots.
"The data may push more patients to consider longer durations of anti-estrogen therapy," said Dr. Harold Burstein, an oncologist at the Harvard Medical School and Dana-Farber Cancer Institute. "Patients will also need to be aware of the trade-offs, including mild side effects and more serious but rare cancer risks."
But Dr. Clifford Hudis of Memorial Sloan Kettering Cancer Center said benefits appear to outweigh the risks.
"The fact that overall survival is improved suggests that whatever the 'cost' from any and all toxicities, they are outweighed by the improvement in breast cancer outcomes," he said.
The promising findings could also support extending other hormone cancer therapies like aromatase inhibitors, which are more commonly used in post-menopausal women.
"The issue really is about which is more effective and less toxic -- longer duration with tamoxifen alone or tamomoxifen and then an aromatase inhibitor," said Dr. Karen Gelmon, a medical oncologist and head of the Investigational Drug Program at the BC Cancer Agency. "This is of interest however for women who remain premenopausal after five years of tamoxifen as longer therapy may be of value."
The tamoxifen findings also highlight the need for longer follow-up after breast cancer trials.
"Many would like to think that five or 10 years out they are safe. But unfortunately there are women who will have a relapse and die from breast cancer," said Dr. Len Lichtenfeld of the American Cancer Society. "And that's why this study is of importance, because this may warrant longer treatment and it shows that in breast cancer, long term trials are important."