The drug, Aromasin, blocks the production of estrogen that's made outside of the ovaries. It's approved by the FDA to reduce the risk of recurrence in certain postmenopausal women who've already been through at least one bout of breast cancer.
The new study, however, suggests it could also be used to prevent malignancies in healthy women who may have an elevated risk because of age, family history, abnormal breast biopsy results, or other reasons.
The study is published in the New England Journal of Medicine and was presented at the 2011 meeting of the American Society of Clinical Oncologists in Chicago. It shows that Aromasin reduced the risk of invasive breast cancer by 65% compared to a placebo.
In light of the study's findings, researchers say they will give now give women in the study who were unknowingly assigned to the placebo a chance to switch to Aromasin as they continue to be tracked for several more years.
Two other drugs, tamoxifen and raloxifene, which block the effect of estrogen on breast cells, are approved for cancer prevention. But tamoxifen can also have serious side effects, including strokes, blood clots, and endometrial cancers. Raloxifene can have side effects including hot flashes, leg cramps, and joint pain.
Because of the side effects, may women shy away from using those drugs. Research suggests that only about 4% of the 2 million women who could benefit from taking tamoxifen to prevent breast cancer choose to do that.
"A pill that may cause cancer as a secondary effect is a hard sell for healthy women," says study researcher Paul Goss, MD, PhD, a professor of medicine at Harvard University and head of breast cancer research at Massachusetts General Hospital in Boston, who spoke at a news briefing.
Risks vs. Benefits
The study shows that Aromasin, which belongs to a class of medications called aromatase inhibitors, appears to reduce the risk of breast cancer more effectively than tamoxifen or raloxifene and has fewer side effects -- a balance of benefits and risks that many think may change women's minds about the idea of taking a medication in advance of a diagnosis.
"It's a potentially game-changing thing," says study researcher Rowan T. Chlebowski, MD, PhD, chief of medical oncology at the David Geffen School of Medicine at the University of California, Los Angeles.
Researchers who weren't involved in the study agree.
"The study speaks for itself. It is remarkably positive," says Marc E. Lippman, MD, chairman of the department of medicine at the Miller School of Medicine at the University of Miami.
Lippman says it remains to be seen whether women will warm to the idea of taking a medication when they're healthy to lower the chance that they may get cancer later, particularly if it means dealing with side effects.
Aromatase inhibitors have been shown to cause some bone loss, which can be reversed, and many women find that symptoms associated with menopause like hot flashes, insomnia, fatigue, and arthritis get worse while on the medications.
In the current study, however, about the same number of women reported those kinds of side effects in the placebo group compared to those taking Aromasin, suggesting little difference on or off the drug.
There were no major differences between the two groups in terms of fractures, cardiovascular events, other kinds of cancer, or treatment-related deaths.
Oncologists say the new study means that more women can, and probably should, be on the medications.
Tracking Breast Cancer Risk
Starting in 2004, researchers enrolled 4,560 postmenopausal women.
In order to be included in the trial, women had to be either over age 60 or they had to be over age 35 with a Gail risk score of 1.66% or higher or have a history of in situ cancer. A Gail risk score calculates the five-year risk of developing breast cancer based things like family history, age, race, and childbearing history.
Women weren't eligible if they were premenopausal, because Aromasin doesn't work in women with functioning ovaries.
They were also excluded if they'd had a diagnosis of invasive breast cancer; were known carriers of the BRCA1 or BRCA2 genes; had history of other kinds of invasive cancer within the last five years; or had uncontrolled thyroid or liver disease.
About half of the women enrolled in the study were over age 60.
The average age of study participants was 62.5 years and the midpoint of their Gail scores was 2.3%.
The women were then randomly assigned to receiver either 25 milligrams of Aromasin daily or a placebo pill. Neither the women nor their doctors knew who was getting treatment or placebo.
Researchers gave the women annual checkups, including a yearly mammogram.
After about three years of follow-up, 43 invasive breast cancers were diagnosed: 11 in the Aromasin group and 32 in the placebo group.
Overall, 0.55% of women in the placebo group and 0.19% of women in the Aromasin group were diagnosed with breast cancer each year during the study, a reduction in risk of about 65% for women taking the drug.
Stated another way, researchers found that 94 women would need to take the drug for three years to prevent one case of cancer. That number dropped to just 26 women to prevent one diagnosis of breast cancer after five years.
The majority of cancers in both groups were estrogen receptor positive, a kind of cancer that tends to respond well to treatment.
In women who had previously used hormone replacement therapy, Aromasin had slightly greater effect, reducing the risk of cancer by 70% compared to placebo.
The study wasn't able to show that the drug improved overall survival, however.
Adverse events were reported by 88% of women on Aromasin and 85% of women taking the placebo.
Arthritis and hot flashes were slightly more common in the treatment group.
There were no differences between the groups in the numbers of women who were newly diagnosed with osteoporosis or cardiovascular events.
Serious adverse events in the study were rare and none were judged to be attributable to Aromasin.
The study was sponsored by the Canadian Cancer Society Research Institute, the Canadian Institutes of Health Research, the Avon Foundation, and Pfizer, the company that makes Aromasin.