By Catherine Arnst
For the past quarter century, the treatment of choice for most breast cancers has been Tamoxifen, made by Astra-Zeneca (AZN ). But a 5000-patient study released on Mar. 10 found that breast-cancer patients who received an estrogen-blocking drug called Aromasin after surgery had significantly fewer recurrences of the disease than those who received the gold-standard Tamoxifen.
The results, published in The New England Journal of Medicine, are the strongest evidence to date that the class of drugs known as aromatase inhibitors, which includes Pfizer's (PFE ) Aromasin, could become the drug of choice for preventing breast-cancer relapses.
"There aren't too many [cancer] studies that come along that are this important," says Dr. Stephen Jones, medical director of U.S. Oncology Research and a co-author of the report. "This really challenges the standard strategy of putting a woman on five years of Tamoxifen."
The report should also give new prominence to the other two main aromatase inhibitors -- Arimidex from Astra-Zeneca and Femara from Novartis (NVS ). The current standard of care for breast cancer calls for surgery followed by five years of treatment with Tamoxifen, a different type of estrogen-blocker. That five-year follow up is important, because the risk of recurrence is highest during this period after diagnosis. About 500,000 women in the U.S. are taking Tamoxifen, which is now a generic drug.
Aromatase inhibitors, approved in the late 1990s, are usually given after the five-year regimen of Tamoxifen to make sure the cancer doesn't return. However, doctors have long suspected they could actually replace Tamoxifen because of the way it deploys in the body.
Tamoxifen is essentially a low-level estrogen that blocks naturally-occurring estrogen from attaching to cells. Aromatase inhibitors block production of aromotase, a substance used by the body to create estrogen. By taking a step back in the estrogen-production process, these drugs avoid some of the side effects of Tamoxifen, such as an increased risk of ovarian cancer. And besides being safer, several trials over the past two years have reported that the newer drugs were also superior to Tamoxifen at preventing recurrences. This latest Aromasin study backs up that conclusion.
The randomized, double-blind study enrolled 4,742 women from 37 countries, all postmenopausal with tumors that were highly sensitive to estrogen. Half the women were kept on Tamoxifen alone for the full five years, while the other half were switched to Aromasin after about 30 months.
Result: Three years later, the patients on Aromasin had a 32% risk reduction of breast cancer recurrence compared to those who remained on Tamoxifen. Ultimately, 91.5% of patients on Aromasin were free of breast cancer five years after surgery, compared with 86.8% of those remaining on tamoxifen. In addition, Aromasin has fewer side effects than Tamoxifen, which can increase the risk of uterine cancer.
This study is similar to one reported in December comparing Astra-Zeneca's Arimidex to Tamoxifen. It found that Arimidex alone prevented more recurrences than Tamoxifen alone, as well as working better alone than when given in combination with Tamoxifen.
Another trial reported last October found that Norvatis' Femara -- given to women with advanced-stage breast cancer -- worked better than Tamoxifen at slowing the progression of the disease. And every study has shown that these three aromotase inhibitors do a better job than Tamoxifen in preventing tumors in the second breast, indicating that they may be effective in preventing cancer altogether in high-risk women.
TOO MANY OPTIONS?
"These three studies taken together indicate that no matter when you start treatment with aromotase inhibitors, patients do a little better than they would with Tamoxifen," says Dr. Clifford Huddis, chief of the breast cancer medicine service at New York's Memorial Sloan-Kettering Cancer Center.
There's still one big question, though: Huddis cautions that oncologists still don't know the best way to use this class of drugs. "We have a lot of options now -- and that's the dilemma," he says. He also notes that none of the aromotase inhibitors have yet proven that they can keep women alive longer than if they stayed on Tamoxifen -- such a survival trial would take several years of followup. Doctors also don't know which of the three aromotase inhibitors might be superior.
Still, the latest news that there are more treatment options can only come as a relief to the more than 200,000 women in the U.S. who will be diagnosed with breast cancer this year.
Arnst covers medicine for BusinessWeek