SUNDAY, May 2, 2004 (HealthDayNews) -- When a woman is diagnosed with breast cancer, she no longer just hears the word "tamoxifen." She's also offered a variety of other drugs that may be of great benefit.
And while it's true this new class of drugs, called aromatase inhibitors, is starting to challenge the 20-year reign of tamoxifen, cancer experts say it's too soon to abandon this stalwart therapy just yet.
"We're in a period of transition, but I think the definitive study still has not been published," said Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in New Orleans. "I still have tended to use tamoxifen as the first-line treatment for women who would be eligible for it. But women who are not able to tolerate it should not fear that they are receiving an inferior drug [with the aromatase inhibitors]."
Tamoxifen first came into widespread use in the 1970s for women who had metastatic breast cancer, where the disease had spread to other parts of their body.
"It was a very effective, safe, well-tolerated drug," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. "It was then and, in general, it is now."
Over the years, tamoxifen's use has been expanded so it is standard to give it to women after their initial treatment of surgery, chemotherapy or radiation to prevent recurrences of the cancer. Studies have shown the drug, which interferes with the ability of the hormone estrogen to fuel tumor growth, can reduce the risk of breast cancer recurrence by 47 percent and the risk of death by 26 percent.
Tamoxifen is also used to reduce the risk of breast cancer in high-risk women who have not yet had the disease. "That's probably the major underutilized use of tamoxifen," Lichtenfeld said. "It reduces the risk of breast cancer in high-risk women by 50 percent."
The drug does have some potential side effects, namely increased risk of uterine cancer and blood clots in the legs. "These risks are negligible, especially in light of the terrible things that can happen in breast cancer," Lichtenfeld said.
In women who are trying to prevent breast cancer and are otherwise healthy, however, the side effects may be more difficult to accept.
Aromatase inhibitors, which work by inhibiting an enzyme called aromatase that helps make estrogen, also can have side effects, including hot flashes and vaginal bleeding. Unlike tamoxifen, these drugs can't be used in premenopausal women who still have their ovaries. So far, three have been approved by the U.S. Food and Drug Administration for use in the United States: anastrazole, letrozole and exemestane.
The data comparing these different compounds with tamoxifen is just starting to emerge.
An early comparison of tamoxifen and anastrazole showed the latter may be superior to tamoxifen as a companion therapy for postmenopausal women. "So far, the data has suggested that anastrozole may be somewhat better," Lichtenfeld said. "Having said that, it takes a long time for these things to work out. It doesn't happen in one, two, three years. Sometimes it takes five, 10, 15 years until we know how much more effective one drug is."
Another study found that adding letrozole after five years of tamoxifen (what is known as sequential therapy) resulted in significant decreases in breast cancer recurrences, compared with women who only took tamoxifen.
Yet another study found that taking exemestane after an initial course of tamoxifen decreased the risk of recurrence and new malignancies in postmenopausal women. But this trial, and others, raises as many questions as it answers. "Is it the combination, the single drug, the duration?" Lichtenfeld asked. "We don't know the answers to those questions."
Given the bulk of the data, Lichtenfeld said, "We're not seeing a wholesale recommendation by experts in the field against tamoxifen. We're still seeing recommendations of tamoxifen as the primary hormonal treatment to be used in the adjuvant therapy of postmenopausal and premenopausal women and aromatase inhibitors to be used for women who can't tolerate tamoxifen and other particular situations."
Dr. Steven Goldstein, a professor of obstetrics and gynecology at New York University School of Medicine, is concerned about the risk of endometrial cancer in women on tamoxifen. He's particularly concerned about women with uterine polyps who take the drug.
"What I now advocate is that people with newly diagnosed breast cancer should have an endometrial evaluation," he said. "If they're squeaky clean, then the risk [of taking tamoxifen] is no greater than the general population. And if they have undiagnosed polyps, remove the polyp but watch more closely."
Aromatase inhibitors are a nice option, experts said, but not one that should replace tamoxifen just yet.
"What we would not say right now is abandon tamoxifen in favor of aromatase inhibitors, except in those women who cannot take tamoxifen," Lichtenfeld said.