Many post-menopausal women take hormonal therapy medicine -- either an aromatase inhibitor or tamoxifen -- after breast cancer surgery and other treatments for hormone-receptor-positive, early-stage breast cancer. Hormonal therapy medicine can reduce the risk of the cancer coming back (recurrence). Hormonal therapy medicine taken after surgery and other treatments is called adjuvant hormonal therapy.
The study reviewed here found that taking the aromatase inhibitor Femara (chemical name: letrozole) as adjuvant hormonal therapy improved overall survival compared to tamoxifen. These results were presented at the 2008 San Antonio Breast Cancer Symposium.
Other research has shown that aromatase inhibitors are somewhat better than tamoxifen at reducing the risk of breast cancer coming back. (Armidex [chemical name: anastrozole] and Aromasin [chemical name: exemestane] are the other two aromatase inhibitors.) Still, the earlier research didn't show that an aromatase inhibitor improved overall survival compared to tamoxifen. The study reviewed here, called the BIG 1-98 trial, is the first study to show an overall survival benefit for the aromatase inhibitor Femara compared to tamoxifen. Overall survival was 13% better in the women who took Femara compared to the women who took tamoxifen.
The researchers compared the risk of breast cancer coming back in women who started taking tamoxifen and then switched to Femara after several years to the risk of breast cancer coming back in women who took only Femara. All of the women took hormonal therapy medicine for a total of 5 years. The results suggest that taking an aromatase inhibitor for 5 years is somewhat better at reducing the risk of breast cancer coming back compared to starting on tamoxifen and then switching to an aromatase inhibitor. After 5 years, 9.1% of the women who started on tamoxifen and then switched to Femara had the breast cancer come back, compared to 7.3% of the women who took Femara for 5 years.
Research continues to show that an aromatase inhibitor is the best hormonal therapy medicine to start with after initial breast cancer treatment for post-menopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer. But tamoxifen is still a good choice, depending on your unique situation. For a number of reasons, including side effects and cost, tamoxifen may be a better choice for some women.
When you're deciding on a treatment plan, keep two things in mind:
If you're a post-menopausal woman being treated for hormone-receptor-positive, early-stage breast cancer, talk to your doctor about the differences in benefits and side effects of aromatase inhibitors and tamoxifen. If you're currently taking tamoxifen, discuss whether switching to an aromatase inhibitor makes sense for you. Together, you can decide on a treatment plan that is best for YOU.
SAN ANTONIO, Dec. 16 (MedPage Today) -- For women with endocrine-responsive early breast cancer, letrozole (Femara) as the initial adjuvant endocrine therapy may modestly improve overall survival compared with tamoxifen.
Five years of letrozole monotherapy increased survival 13% in the intent-to-treat analysis (P=0.08) and a significant 19% in an analysis censored for extensive "contamination" by off-protocol switching from tamoxifen to letrozole, Henning Mouridsen, M.D., of Rigshospitalet in Copenhagen, reported at the San Antonio Breast Cancer Symposium.
Both analyses of the randomized controlled Breast International Group (BIG) 1-98 trial were likely to be biased by the selective crossover such that the "true" survival benefit is between the two, Dr. Mouridsen said.
He and Alan Coates, M.D., of the University of Sydney in Australia, who presented the results at a press conference, said they were convinced that the survival advantage suggested by the findings was real.
If so, it would be the first time an aromatase inhibitor has shown the expected impact on all-cause mortality compared with tamoxifen in this setting, they said.
Given these findings, Dr. Coates said five years of upfront letrozole rather than tamoxifen should be the standard of care.
He recommended that initial tamoxifen be considered only for the "small group of very, very low risk patients, if you can identify those groups," and patients who cannot afford the more expensive aromatase inhibitor.
Earlier studies comparing a switch strategy of two to three years of tamoxifen followed by an aromatase inhibitor through five years have demonstrated overall survival advantages, Dr. Coates noted.
In fact, many oncologists thought the sequence would turn out better than monotherapy -- a question also investigated by BIG 1-98, he said.
After the initial reports in 2005 showed that letrozole prolonged disease-free survival and reduced risk of distant metastases, Dr. Mouridsen and colleagues randomized 3,088 patients of the 8,010 postmenopausal women with receptor-positive breast cancer included in the trial to two years of tamoxifen followed by three years of letrozole or vice versa.
However, neither switch strategy tested in BIG 1-98 improved on straight letrozole in the study.
At a median 76 months of follow-up, five years of letrozole was associated with the following in comparison to tamoxifen monotherapy:
By comparison, patients who switched to letrozole from tamoxifen tended to have a higher risk of recurrence than those who started with letrozole (9.1% versus 7.3% at five years).
The early separation in event rates on Kaplan-Meier curves favoring letrozole over tamoxifen remained over time, Dr. Coates noted.
Similar trends favored upfront letrozole for disease-free survival and time to distant recurrence.
"I think a lot of people looking at those graphs will take the clinical message that it's better to start with letrozole, particularly for patients at high risk," he said.
But there was no consistent trend for a difference in any of the outcomes for letrozole compared with the group that started on letrozole and switched to tamoxifen.
This is good news for patients, Dr. Coates said. Patients who need to switch back from letrozole to tamoxifen because of side effects or cost can do so without compromising outcomes, he noted. "If you can only afford or tolerate a few years of letrozole, it's better up front."
This patient care aspect is critical, commented Susan Love, M.D., of the University of California Los Angeles and moderator of the press conference.
Although cautioning physicians not to over-interpret these switch data, she said it's reassuring that "the difference isn't that large -- patients aren't taking their life in their own hands" by deciding to switch to tamoxifen.
Both presenters acknowledged the biased nature of both intent-to-treat analyses, which Dr. Coates called "legitimate but contaminated," and censored analyses, which he called "maybe the best approach we've got but biased the other way."
Overall, 25.2% of patients randomized to tamoxifen monotherapy received letrozole after unblinding of this group (the three other treatment groups remained blinded).
This problem has muddied the waters of other aromatase inhibitor/tamoxifen trials as well.
"It isn't a completely solved statistical problem, and I don't think it's completely solvable," Dr. Coates concluded.
The study was funded by Novartis and coordinated by the International Breast Cancer Study Group.
Dr. Mouridsen reported receiving fees from Novartis for advisory boards and lectures.
Dr. Coates provided no information on conflicts of interest.
Dr. Love reported being president of the Dr. Susan Love Research Foundation and the Love/Avon Army of Women and has previously reported conflicts of interest with Windy Hill Medical.
Primary source: San Antonio Breast Cancer Symposium Source reference: Mouridsen HT, et al "BIG 1-98: A randomized double-blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer" SABCS 2008; Abstract 13.
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