The results mark a highly anticipated advance toward the elusive goal of offering women the first safe way to protect themselves from a leading cancer killer. Women have long been able to take an older class of anti-estrogen drugs to reduce their risk, but
few do because of possible side effects, which include uterine cancer and potentially life-threatening blood clots. Many experts had hoped aromatase inhibitors would offer a safer, more acceptable alternative. The new study was the first time one had been tested.
“This is a major step forward,” Larry Norton, a breast cancer expert at Memorial Sloan-Kettering Cancer Center in New York who was not involved in the research, wrote in an e-mail. “This is a long-awaited report from [among] the most highly-respected investigators in the field concerning a critically important topic in cancer prevention.”
Some breast cancer patient advocates and other experts, however, remained cautious. While a 65 percent reduction in risk is significant, the absolute risk for these women remains small. And although aromatase inhibitors do not appear to cause uterine cancer or blood clots, the long-term safety of medicating otherwise vibrant women for many years remains far from clear, some experts say.
“They may be high-risk, but they do not have diagnosed breast cancer. So we are giving thousands of healthy women a drug with side effects, and that has to be very carefully balanced against the benefit and the magnitude of any benefit,” said Fran Visco, president of the National Breast Cancer Coalition, a Washington-based advocacy group.
Breast cancer strikes more than 200,000 women in the United States each year and kills more than 40,000, making it the most common cancer among women after skin cancer and the second-leading cancer killer.
Surgery, radiation, chemotherapy and estrogen-blocking drugs have cut the breast cancer death rate. But researchers, women’s health advocates and patients have been trying to find ways to prevent the cancer. Some women at high risk become so anxious that they voluntarily have their breasts surgically removed even before they have been diagnosed with a tumor.
“This intervention offers women perhaps a more palatable option,” said Andrew D. Seidman, a breast cancer expert speaking on behalf of the American Society for Clinical Oncology, which sponsored the annual meeting of cancer specialists in Chicago at which the results were unveiled. The findings were posted online by the New England Journal of Medicine, which also offered a strongly worded editorial endorsing the results.
“It’s a significant development,” Seidman said.
The drugs tamoxifen and raloxifene, which stop estrogen from fueling breast cancer cells, have long been known to reduce the chances of getting the disease or suffering a recurrence, but they are risky. Aromatase inhibitors, sold under the names Aromasin, Femara and Arimidex, prevent estrogen from being formed.
Attempts to test aromatase inhibitors to prevent breast cancer have been controversial, however. In 2007, the National Institutes of Health canceled a $100 million study, citing the cost, patients’ and doctors’ lack of enthusiasm for the tamoxifen and raloxifene therapies, and other factors.
“This should be considered good news for postmenopausal women who are at risk for getting the disease,” said Leslie G. Ford, a cancer prevention expert at the National Cancer Institute. “Preventing breast cancer or reducing a woman’s risk of getting breast cancer is a very important pursuit. This is another step in the process, and an important one for postmenopausal women.”
In the new study, 4,560 women in the United States, Canada, Spain and France daily took 25 milligrams of Aromasin, which is known generically as exemestane, or a placebo. All the women were considered in danger of getting breast cancer because they were at least 60, had a close relative who had the disease, or scored high on a commonly used risk assessment scale
. The study was partially funded by Pfizer, which makes exemestane, but conducted independently by the Canadian Cancer Society’s NCIC Clinical Trials Group.
The researchers initially planned for the study to run five years, but they discontinued the experiment after about three when they found the clear imbalance of invasive breast cancers among the women who took Aromasin versus those who got a placebo. There were 32 cases of invasive cancer among the women getting placebos and only 11 among those taking Aromasin, indicating the drug’s protective effect was stronger than that of tamoxifen or raloxifene.
In addition, women taking Aromasin were less likely to develop abnormal lesions that can become cancerous, very early cancers and the most deadly types of tumors.
“This is a big deal,” said Paul E. Goss, a professor of medicine at the Harvard Medical School and Massachusetts General Hospital in Boston who led the study. “I think it’s probably the most important news in breast cancer chemo-prevention ever. Any woman who is at increased risk should consider this an excellent option.”
Although aromatase inhibitors are only helpful for women who have already gone through menopause, most breast cancers occur among older women. Because the drug has already been approved to treat breast cancer and prevent recurrences, it is available for doctors to use for this purpose.
Those taking Aromasin were more likely to have hot flashes, fatigue, sweating, insomnia and muscle and joint pain. But they reported that those side effects did not significantly reduce their quality of life, Goss said.
There were concerns the drug would increase the risk for bone fractures, but that turned out not to be the case, he said.
“The drug appears to be very safe and has a very clean safety profile,” Goss said.
Others, however, cautioned that many questions remain. Three years is far too short to know for certain that the drug does not thin bones or whether the drug may cause other dangers, such as heart problems, experts said. And no one knows whether such treatment actually leads to fewer deaths.
“We need longer follow-up to be sure of the absence of long-term ill effects, but the results at 35 months of median follow-up are certainly encouraging in this regard,” Norton said.
The study was among dozens discussed Saturday at the Chicago meeting. Researchers also presented data indicating that some breast cancer patients could benefit from additional radiation treatment and that the drug Avastin may slow the progression of ovarian cancer.