Raloxifene reduces breast cancer risk in postmenopausal women at all risk levels

September 13, 2006

PHILADELPHIA - 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.
-end-
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.

*Editors Note: For a PDF of the study, please e-mail decicco@aacr.org.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 other countries.

AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care.

AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

American Association for Cancer Research

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.