The study is expected to change the way doctors prescribe tamoxifen, a drug that blocks the effects of estrogen on breast cells. About 80% of all breast cancers are sensitive to the hormone estrogen for growth.
The research also hints that longer courses of other kinds of hormone-reducing medications may also work better than shorter courses after breast cancer surgery, though trials testing that theory are ongoing.
“I think the result of this trial will have a major immediate impact on premenopausal women,” says Peter Ravdin, MD, PhD. Ravdin is the director of the Breast Health Clinic at the Cancer Therapy and Research Center at the University of Texas Health Science Center, in San Antonio.
Newer kinds of estrogen-reducing drugs, called aromatase inhibitors, have largely replaced tamoxifen as the preferred therapy for postmenopausal women with estrogen-sensitive cancers. This study won’t change that.
But those kinds of drugs don’t work for women before menopause. For them, doctors still recommend taking tamoxifen.
Current guidelines recommend that women stop tamoxifen after five years because the drug increases the risk of uterine cancers and dangerous blood clots.
The new study found small increases in cases of uterine cancer in women who took the drug for an additional five years. Those women also had slightly higher risks of developing a blood clot in their lungs. But those additional risks did not appear to outweigh the survival benefits of staying on the drug.
“I think that for women who are now approaching five years of therapy, where we’d usually be telling them — up to this point — that we’re going to be stopping the tamoxifen, now we’re going to be telling them that there is clinical evidence that 10 years is superior to five years, and I’m going to be comfortable doing that,” says Ravdin, who led a news briefing on the study but was not involved in the research.
The study was published in the Lancet and presented to doctors at the 2012 San Antonio Breast Cancer Symposium.
Testing Longer Courses of Tamoxifen
The study compared nearly 7,000 women with early-stage, estrogen-sensitive breast cancers. Early-stage cancers were considered to be any cases in which all detected disease could be completely removed.
About half the women in the study stopped taking tamoxifen after the recommended five years, while the other half took the drug for 10 years.
Over the next 10 years, 1,328 women in the study saw their cancer recur. There were 617 recurrences in the group that took tamoxifen for 10 years compared to 711 among women who took the drug for five years. Overall, women who stayed on tamoxifen cut their risk of having cancer come back from 25.1% to 21.4%
There were also fewer deaths from breast cancer in the group that stayed on tamoxifen — 12.2% in the 10-year group compared to 15% in the 5-year group.
“It’s a small extra gain. I don’t want to oversell it. It’s small, but it’s real,” says researcher Richard Peto, a professor of medical statistics and epidemiology at the University of Oxford in the U.K.
“I suspect it will affect the treatment of hundreds of thousands of women worldwide, and it will avoid a few thousands deaths each year worldwide,” he says.
Benefits Greatest in the Second Decade After Diagnosis
The biggest differences between the two groups were seen in the second decade after diagnosis.
For example, other studies have found that women who take tamoxifen for five years can cut their risk of dying of breast cancer by about 30% in the decade that spans 10 to 20 years post-diagnosis, compared to not taking the drug at all.
The new study suggests that women who continue to take tamoxifen for another five years may reduce that risk even further, by an additional 30%.
Researchers estimate that women with early estrogen-sensitive tumors who take tamoxifen for a full 10 years would have about half the risk of dying of breast cancer in the second 10 years after diagnosis compared to women who don’t take the drug.
“You’re holding down the disease that’s scattered around the body and this produces benefit years and years after the treatment is finished,” Peto says.
This isn’t the first study to test the effects of longer courses of tamoxifen. Previous studies had mixed results. Some concluded that the additional risks of the drug didn’t outweigh its benefits, but those studies were much smaller and had limited power to see differences between their study groups.
Peto notes that they did see slightly more cases of uterine cancer and blood clots in women who doubled their time on tamoxifen — 1.6% of women in the five-year group were diagnosed with uterine cancer compared to 3.1% in the 10-year group.
There were about twice as many cases of pulmonary embolism, cases where a dangerous blood clot makes its way to the lungs — 21 in the five-year group as opposed to 41 in the 10-year group. There was no significant increase in stroke risk.
Study May Herald a Shift in Thinking About All Kinds of Hormone Treatments
Experts who were not involved in the study said it was likely to have a limited application, partly because newer drugs have displaced tamoxifen in older women and partly because it can be a difficult drug to take.
“I think there’s a group of women who are very concerned about recurrence and feel that if they can do anything to decrease their risk, that may be worth it for them,” says Jennifer Litton, MD, an assistant professor in the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.
“Then there are a lot of other patients I have who are having side effects — hot flashes and other issues — who are counting the minutes to get off it.” For them, Litton says the additional benefits may not seem worth it.
Ravdin agrees that continuing treatment is likely to be a highly individual choice.
But he says the study is also important because of what it seems to signal about the biology of the disease.
“There are some people slated to have late relapses that our early therapies aren’t effective for blocking, but we can do better by actually treating women with additional hormonal therapy beyond five years, and that can be important,” Ravdin says.
The researchers agree.
“It encourages one to hope that any form of [hormone] treatment, whether it’s aromatase inhibitors or tamoxifen, might be more effective with longer treatment,” says researcher Richard Gray, MSc, of the clinical trials services unit at the University of Oxford.