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Letrozole tops Tamoxifen for early breast cancer treatment

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The breast cancer drug letrozole, marketed as Femara, may be more effective than tamoxifen at preventing the return of breast cancer and improving survival among older women with hormone-sensitive breast cancers, a new study reports.
In the study, published online Oct. 21 in The Lancet Oncology, the researchers updated data from an ongoing study of about 8,000 women, which compares the two drugs alone as well as the use of both Femara and tamoxifen sequentially.
Femara outperformed tamoxifen in terms of breast cancer recurrence and survival, the study found. Moreover, giving Femara alone to women was more effective than giving it sequentially following tamoxifen. The new study was partially funded by Novartis, the drug company that makes Femara.
The hormone estrogen feeds hormone-sensitive cancers, and blocking it may help stave off a recurrence. Femara is part of a class of breast cancer drugs known as aromatase inhibitors. These drugs block the body's production of estrogen via the enzyme aromatase. Tamoxifen is a selective estrogen receptor modulator, which means that it acts like estrogen in certain tissues, but not in others, namely the breast. Aromatase inhibitors are given alone or in combination with tamoxifen.
After an average eight years of follow-up, the team of researchers from the United States, Europe and Australia found that women who took Femara for five years after breast cancer treatment had a "20 percent reduced risk of their breast cancer coming back and were 21 percent less likely to die, compared with women given tamoxifen alone," one of the lead authors of the study, Meredith Regan of the Dana-Farber Cancer Institute in Boston, explained in a journal news release.
Neither sequential treatment of tamoxifen followed by Femara, or in the reverse order, significantly decreased the likelihood of relapse or death compared to Femara alone, the team reported.
"Femara alone is the best way to go," said Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City. "The hope was that the combination would improve survival, but this was not the case," said Bernik, who was not involved with the study.
Breast cancer survivors who are being treated with tamoxifen should discuss their options with their doctor. "Talk to your doctor about switching to an aromatase inhibitor," Bernik said. "Tamoxifen is still an excellent drug, but the aromatase inhibitors are better. If the plan was to switch drugs, you may want to talk to [your] doctor about going straight to the aromatase inhibitor," she added.
Dr. Hannah Linden, a medical oncologist at the Seattle Cancer Care Alliance, said that many women don't want to take these drugs because of a fear of side effects or the desire to put breast cancer behind them. "The study stresses the importance of taking these medications," she said. This is not to say they don't have their share of side effects; they do, she noted.
Serious side effects seen with Femara include bone fractures and increases in cholesterol levels. Some research has suggested that aromatase inhibitors may also increase the risk for heart disease. Tamoxifen side effects may include blood clots, strokes, uterine cancer and cataracts.
Dr. Maura N. Dickler, a breast cancer medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, said that aromatase inhibitors have been her go-to drugs for women with estrogen-positive breast cancers for a while.
Some women report joint pain and other nuisance side effects from aromatase inhibitors and have to go back to tamoxifen, Dickler said. "In these cases, getting in an aromatase inhibitor for some time is beneficial," she noted. "We can individualize treatment based on the side effects and the tolerability for each woman."
Cost may be an issue for some women, but the gap in price between the two drugs is narrowing, Dickler added. Femara is now available as a generic, which helps reduce its costs, but tamoxifen is still probably less expensive, she said.
Overall, "this is an exciting update with longer follow-up," Dickler said of the study. Since last results were reported in 2005, there was a 32 percent increase in the number of women who had a relapse. "These women can do well for a long time and still relapse many years later," she said. "It just reminds us that women relapse during year five through 10 as much as zero through five. Breast cancer is an indolent disease and you can remain disease free for a long time, but relapse can still happen."
 
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