Tamoxifen and aromatase inhibitors, two types of hormonal therapy medicines, usually are taken for 5 years after surgery (and possibly radiation and chemotherapy) to lower the risk of hormone-receptor-positive, early-stage breast cancer coming back in post-menopausal women. Because the hormonal therapy medicines are taken after surgery, they're called adjuvant hormonal therapy.
The study reviewed here adds more evidence to support the current standard of care for post-menopausal women diagnosed with early-stage hormone-receptor-positive breast cancer: aromatase inhibitors are somewhat better than tamoxifen at reducing the risk of breast cancer coming back, as well as at improving overall survival in some cases. These results were presented at the 2008 San Antonio Breast Cancer Symposium.
Tamoxifen and the aromatase inhibitors work in different ways to lower the risk of breast cancer coming back (recurrence). Tamoxifen blocks the effects of estrogen on breast cancer cells. Aromatase inhibitors lower the amount of estrogen in the body. The aromatase inhibitors are:
The researchers looked at the results from nearly 10,000 women who participated in several studies comparing individual aromatase inhibitors to tamoxifen. In the studies, the women usually were given tamoxifen alone or an aromatase inhibitor alone for 5 years. In some cases the women began the study taking tamoxifen and then switched to an aromatase inhibitor.
Overall, aromatase inhibitors were 23% better than tamoxifen at reducing the risk of breast cancer coming back. Aromatase inhibitors offered different amounts of risk reduction depending on the specific location of the cancer coming back. Compared to tamoxifen, aromatase inhibitors were:
While aromatase inhibitors improved overall survival compared to tamoxifen, this increase could have been due to chance.
Women who started taking tamoxifen and then switched to an aromatase inhibitor also had a lower risk of the cancer coming back and improved overall survival.
Still, the advantages of aromatase inhibitors compared to tamoxifen diminish over time. While breast cancers that are going to come back usually do so in the first 3 years after diagnosis, recurrence can happen any time after breast cancer treatment. Some doctors recommend that hormonal therapy be taken for more than 5 years to further reduce the risk of the cancer coming back later.
Both tamoxifen and aromatase inhibitors can cause side effects. Tamoxifen may cause hot flashes. Aromatase inhibitors may cause muscle and joint pain and sometimes hot flashes. Aromatase inhibitors also can weaken bones, while tamoxifen actually can strengthen bones.
While aromatase inhibitors have clear advantages, tamoxifen may be a better choice for some women because of side effects and cost. Some doctors will recommend starting on one type of hormonal therapy medicine and then switching to another type after a few years.
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 pros and cons of aromatase inhibitors compared to tamoxifen. If you're currently taking tamoxifen, discuss whether switching to an aromatase inhibitor makes sense for your unique situation. Together, you can decide on a treatment plan that is best for YOU.
SAN ANTONIO, Dec. 12 (MedPage Today) -- Whether breast cancer patients start on adjuvant aromatase inhibitors, or switch to them later, they lead to a lower risk of recurrence than tamoxifen, and, for some, better survival, researchers said here.
In a meta-analysis across agents, five years on an aromatase inhibitor reduced recurrence an absolute 2.9% with a nonsignificant 1.1% absolute reduction in breast cancer mortality compared with tamoxifen, James Ingle, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues reported at the San Antonio Breast Cancer Symposium.
Women who switched to an aromatase inhibitor after two or three years of tamoxifen had a 29% proportional reduction in recurrence and a significant 0.7% absolute reduction in breast cancer mortality three years later compared with women who stayed on tamoxifen.
"It does not appear that there's any subset of patients who don't get benefit from the aromatase inhibitors," Dr. Ingle said.
These findings summing up the worldwide prospective experience comparing the two classes of endocrine therapy should erase any doubts that aromatase inhibitors are the "somewhat better" choice, he said.
Even though the individual trials seem large enough to answer questions on their own, tamoxifen-treated patients do so well that it takes very large studies, such as the meta-analysis, to get enough events to properly power subgroup analyses, added co-author Mitch Dowsett, Ph.D., of the Royal Mardsen Hospital in London.
So their group pooled data from all trials started by 2000, prospectively comparing an aromatase inhibitor and tamoxifen. Unpublished data from the ABCSG VIII and BIG 1-98 trials were not included.
Among the 9,856 patients who received therapy in trials directly comparing five years of monotherapy, recurrence rates were uniformly lower with aromatase inhibitors.
Aromatase inhibitors were associated with an absolute 2.9% lower recurrence rate at five years that improved to a 3.9% gain at eight years (15.3% versus 19.2%, P<0.00001).
The annual event rate ratios revealed the following compared with tamoxifen:
Mortality analyses showed small, nonsignificant advantages to five years of aromatase monotherapy with gains of 1.1% and 0.5% for five- and eight-year breast cancer mortality and 0.8% and 0.2% gains, respectively, for all-cause mortality.
Dr. Ingle noted that the mortality data were still relatively early with a mean follow-up of 3.9 years. He also noted that tamoxifen's survival advantage at five years was only one-third of what it was at 15 years.
For the 9,015 patients in the pooled analyses comparing tamoxifen monotherapy and two to three years of tamoxifen followed by two to three years aromatase inhibitor, recurrence again was uniformly significantly superior for the group that switched.
These findings included 29% lower overall annual recurrence event rates (P<0.00001) with an absolute gain of 3.1% at three years after the switch and 3.5% at six years after switching (P<0.00001).
The switch cohort showed absolute benefits in the following mortality outcomes as well:
The reason for the difference in mortality benefits between cohorts might have been because some patients about ready to progress on tamoxifen were salvaged when they switched to an aromatase inhibitor, Dr. Ingle suggested.
The advantage of aromatase inhibitors over tamoxifen fell over time in both cohorts, which he said highlights the major remaining question with these agents -- duration of adjuvant therapy.
But all age, nodal status, and tumor grade subgroups showed benefits. The only factor with significant heterogeneity was progesterone receptor status in the monotherapy cohort, which Dr. Ingle said could have been a chance finding.
Dr. Ingle reported no conflicts of interest. Dr. Dowsett reported conflicts of interest for Novartis and AstraZeneca. Co-authors also reported conflicts of interest for AstraZeneca.
Primary source: San Antonio Breast Cancer Symposium Source reference: Ingle JN, et al "Aromatase inhibitors versus tamoxifen as adjuvant therapy for postmenopausal women with estrogen receptor positive breast cancer: meta-analysis of randomized trials of monotherapy and switching strategies" SABCS 2008; Abstract 12.
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