Raloxifene protects postmenopausal women from developing invasive breast cancer whether they are at high or low risk of developing the disease, according to a new study.
The study, published in the September 1 issue of Clinical Cancer Research, also revealed that the drug appears to reduce risk in women with a family history of breast cancer down to a similar level to women without affected relatives.
Compared with a placebo drug, the study found that use of raloxifene was associated with a 58 percent reduction in breast cancer risk in women without a family history of the disease, and an 89 percent reduction in risk for women with a family history of breast cancer.
But the researchers say they cannot explain why protection seems greatest in women who may be genetically predisposed to develop the disease.
"We don't know what to make of this observation," said Marc E. Lippman, M.D., professor in the Department of Internal Medicine at the University of Michigan and the study's lead author. "It could be due to chance, or there may be other factors at work that we don't know about."
"But our bottom-line analysis as to why raloxifene universally reduces the risk of developing invasive cancer in women without a family history is that it interferes with the duration and concentration of estrogen, which acts as a tumor promoter in the majority of breast cancers," said Dr. Lippman.
The research team conducted a new analysis of the first large study of raloxifene, which tested the ability of the drug to prevent vertebral fractures in 7,705 postmenopausal women diagnosed with osteoporosis. The secondary endpoint of this multi-center, double-blind trial, known as MORE (Multiple Outcomes of Raloxifene Evaluation) was the drug's effect on breast cancer development; results, announced in 1999, demonstrated a 72 percent reduction in invasive breast cancer incidence after four years of raloxifene treatment, compared to use of a placebo.
The MORE trial was then extended four years to further evaluate the effect of raloxifene on breast cancer incidence in 4,011 of the original participants. Results of this trial, known as CORE (Continuing Outcomes Relevant to Evista), showed that eight years of raloxifene treatment was associated with a 66 percent decrease in invasive breast cancer incidence.
The current study was undertaken to assess the effect of raloxifene on level of breast cancer risk (higher versus lower) using data from both MORE and CORE.
Women at higher risk for breast cancer are generally older and have a greater lifetime exposure to estrogen, and the researchers found that this association held true in the reanalysis. But they also found that raloxifene reduced breast cancer risk in both women at lower and those at higher breast cancer risk, except for those women who had measurably low levels of estradiol, the major estrogen hormone in humans.
"In each variable commonly associated with a higher risk for developing breast cancer − age older than 65, age at menopause, a body mass index greater than 25, higher estradiol levels, prior use of estrogen replacement and a family history of breast cancer − use of raloxifene reduced incidence of breast cancer when compared to a placebo drug," Dr. Lippman said. "But it also reduced incidence in each of those variables that should have lowered risk, such as younger age, later menopause, etc., compared to use of a placebo drug."
"We don't define the lowest limit of risk, the point at which toxicity associated with use of raloxifene outweighs the benefits," he said.
Dr. Lippman stressed that he cannot comment on how raloxifene in this study measures up to tamoxifen use in general. He explains that although these findings come on the heels of the June publication of the 19,747-participant STAR trial, which evaluated tamoxifen against raloxifene in reducing breast cancer risk, no comparison can be made between the MORE, CORE and STAR clinical trials.
"These studies looked at two different groups of women," Dr. Lippman said. "Women enrolled in STAR were at high risk for developing breast cancer, so presumably, they had higher levels of estrogen in general. Women who participated in MORE and CORE were older and had osteoporoses and it is assumed that these women generally have lower levels of estrogen, because that is a risk factor for development of the disorder."
Raloxifene, also known by the trade name Evista, has not been approved by the federal Food and Drug Administration as an agent to prevent breast cancer development.
Co-authors of the study include investigators from the University of Pittsburgh, the Angeles Clinic and Research Institute, California Pacific Medical Center Research Institute, and Eli Lilly & Company, which manufactures raloxifene.