Postmenopausal breast cancer patients who switch from tamoxifen therapy to a new class of drugs called aromatase inhibitors may live longer. 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 are 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.
Background
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%, according to the study led by Dr. Francesco Boccardo of the National Cancer Research Institute and University of Genoa.
Aromatase inhibitors are a newer class of drugs with a different mechanism. These medicines, which include letrozole (Femara), exemestane (Aromasin), and anastrazole (Arimidex), fight cancer cell growth by blocking the workings of an aromatase enzyme while also reducing estrogen.
The Study
To find out if aromatase inhibitors are more effective and safer than tamoxifen, Boccardo and his colleagues conducted two trials involving a total of 828 postmenopausal Italian breast cancer patients.
Half the patients were given a five-year regimen of tamoxifen, while the other half were switched to a therapy involving one of two aromatase inhibitors around two to three years into their tamoxifen treatment.
Two aromatase inhibitors, aminoglutethimide and anastrozole, were tested. Aminoglutethimide is no longer available for the treatment of breast cancer.
Results
By pooling the results of the two trials, 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 an aromatase inhibitor.
Boccardo and his associates also observed fewer deaths from either stroke or cardiovascular causes among the women who jumped to aromatase inhibitors.
Reaction
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.
Freedman's own research suggested that depending on disease severity, patient age and other factors, not all breast cancer survivors who've completed five years of tamoxifen would 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 US, that among postmenopausal patients, aromatase inhibitors are more effective in increasing survival than tamoxifen."
Cassell pointed out that current protocols among US oncologists have already shifted to ward 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.
Precautions
But, while aromatase inhibitors offer clear survival advantages, new concerns are surfacing, 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."
