Newer Drugs Beat Tamoxifen for Breast Cancer Survival

Aromatase inhibitors may also be safer over the long term, study suggests

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HealthDay Reporter

MONDAY, Feb. 12, 2007 (HealthDay News) -- Postmenopausal breast cancer patients who switch from tamoxifen therapy to another type of drug, called an aromatase inhibitor, may gain a significant boost in survival, Italian research shows.

Women in the study made the switch two to three years into the typical five-year tamoxifen regimen, which is aimed at keeping recurrent breast cancer at bay.

According to the researchers, the improved performance of aromatase inhibitors means patients may also avoid the increased risk of death from other causes -- such as stroke or endometrial cancer -- that have been associated with tamoxifen.

"There's still a lot of questions that remain, but this study confirms that five years of tamoxifen alone is really becoming the wrong answer for most postmenopausal women," said Dr. Gary M. Freedman, a radiation oncologist at the Fox Chase Cancer Center in Philadelphia. "At this point, you have to say that aromatase inhibitors are in the mix of treatment at some point," said Freedman, who was not involved in the trial.

The study, led by Dr. Francesco Boccardo of the National Cancer Research Institute and University of Genoa, was expected to be published in the March 15 issue of Cancer.

Tamoxifen has been in widespread use among breast cancer survivors for the last two decades. The drug is typically taken after surgery, because it targets the hormone estrogen, which can promote tumor cell growth in women with estrogen-sensitive breast cancer. A standard five-year treatment of tamoxifen has been found to reduce breast cancer death rates by as much as 31 percent, Boccardo's team noted.

But aromatase inhibitors are a newer class of drugs. These medicines, which include Femara, Aromasin, and Arimidex, fight cancer cell growth in a different way by blocking the workings of an aromatase enzyme while also reducing estrogen.

But are these drugs better and safer than tamoxifen? To find out, Boccardo and his colleagues conducted two trials involving a total of 828 postmenopausal Italian breast cancer patients followed between 1992-2002.

Half the patients were given a five-year regimen of tamoxifen, while the other half were switched to a therapy involving one of two different aromatase inhibitors at some point, usually two to three years into their tamoxifen treatment.

Two aromatase inhibitors were tested, anastrozole (ANA) and aminoglutethimide (AG). AG is no longer available for the treatment of breast cancer.

By pooling the results of the two trials together, the authors concluded that death rates due to either breast cancer or any other cause significantly improved among the patients who switched to an aromatase inhibitor.

Among full-treatment tamoxifen patients, 74 deaths were reported, of which 51 were breast cancer-related.

In comparison, 48 deaths -- of which 33 were breast cancer-related -- were reported among the group that switched to aromatase inhibitor.

Boccardo and his associates also observed fewer deaths from either stroke or cardiovascular causes among the women who jumped to aromatase inhibitors.

Freedman stressed that the study did not answer questions regarding how long aromatase inhibitors should be used for optimum effect, or whether using them before or after a tamoxifen regimen would be the best way to go.

His own research, published in the journal Cancer in December, suggested that depending on disease severity, patient age and other factors, not all breast cancer survivors who've completed five years of tamoxifen will benefit from aromatase inhibitors.

"So, while in our clinical practice only premenopausal women are being recommended a full five years of tamoxifen alone, I would still say that the decision whether and when to switch to aromatase inhibitors needs to be based on the individual patient," Freedman said.

Dr. Lauren Cassell, a breast surgeon at Lenox Hill Hospital in New York City, said the Italian study reaffirms recent research.

"This finding is not surprising," she said. "There is a consensus, at least in the U.S., that among postmenopausal patients, aromatase inhibitors are more effective in increasing survival than tamoxifen. So, I don't think this study changes anything."

Cassell pointed out that current protocols among U.S. oncologists have already shifted toward excluding tamoxifen from newly prescribed treatment regimens in favor of aromatase inhibitors. And, most patients who are on tamoxifen treatment are now being switched over to the aromatase option, she said.

But, while aromatase inhibitors offer clear survival advantages, new concerns are arising, Cassell added.

"While aromatase inhibitors don't increase the risk for endometrial cancer or stroke associated with tamoxifen, they do increase the risk for osteoporosis and, in some cases, significant joint pain," she said. "And, they are much more pricey than tamoxifen, which is a problem for older patients on fixed incomes who don't have insurance."

More information

For additional information on tamoxifen and aromatase inhibitors, visit the American Cancer Society.

SOURCES: Gary M. Freedman, M.D., radiation oncologist, Fox Chase Cancer Center, Philadelphia; Dr. Lauren Cassell, M.D., breast surgeon, Lenox Hill Hospital, New York City; March 15, 2007, Cancer.

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