The pathway of estrogen metabolism affects breast-cancer risk, UB research shows

October 16, 2000

BUFFALO, N.Y. -- Researchers at the University at Buffalo have found that the development of breast cancer appears to be related to how the body breaks down estrogen.

In only the second prospective study to investigate the role of estrogen metabolism as a predictor of breast cancer, the researchers found that premenopausal women show a 40-percent lower risk of the disease if their predominant pathway of estrogen metabolism produces by-products with little biologic activity, rather than by-products that are highly reactive.

Results of the study appear in the November issue of Epidemiology.

The research is based on data from 10,786 women who took part in a prospective study of breast cancer in Italy called the Hormones and Diet in the Etiology of Breast Cancer (ORDET) study. Paola Muti, M.D., now associate professor of social and preventive medicine at the University at Buffalo School of Medicine and Biomedical Sciences, was principal investigator on that study.

Estrogen must be eliminated from the body once it has performed its essential hormonal duties. High levels of estrogen are known to be a risk factor for cancer and too much also upsets the body's delicate hormonal balance. In order to be eliminated from the body, estrogen undergoes a process called hydroxylation. These hydroxilated estrogens, called estrogen metabolites, can travel easily in the blood stream and be eliminated through the urine.

"Estrogen hydroxylation takes place at two primary sites on the estrogen molecule, designated as the C-2 position and the C-16 position," Muti said. "Earlier research has shown that hydroxylation at the C-2 position produces metabolites with little or no estrogenic activity and thus might be associated with decreased breast-cancer risk. Conversely, hydroxylation at the C-16 position produces metabolites with high estrogenic activity, and might be associated with increased breast-cancer risk.

"We set out to determine if there was an association between later development of invasive breast cancer and the ratio of C-2 to C-16 by-products present in women before cancer developed."

Researchers collected urine samples from all participants when they enrolled in the study and froze them for later analysis. Women with a history of cancer and those with other relevant conditions had been eliminated from the study. After approximately five years, researchers determined that 144 women had developed breast cancer, and they selected four times that number of women from the study who had not developed cancer to serve as controls. Researchers then analyzed the urine samples from both cases and controls to determine the predominant estrogen-metabolism pathway.

Results showed that the premenopausal women who developed breast cancer had a higher percentage of the highly active by-products of estrogen metabolism (produced by the C-16 pathway), than by-products from the C-2 pathway. Women with predominately C-2 pathway by-products (those with low activity) were 40 percent less likely to have developed breast cancer during those five years.

"The way to change from one pathway to the other is through changes in lifestyle," said Muti. "Physical activity and eating a diet low in fat and high in cruciferous vegetables can shift estrogen metabolism from high-risk to low-risk."

Muti and colleagues will continue to investigate why one pathway increases breast-cancer risk and the other does not.
-end-
Also participating in the study were Jo L. Freudenheim, Ph.D., Holger Schunemann, M.D., Jun Yang, M.D., and Maurizio Trevisan, M.D., of the UB Department of Social and Preventive Medicine; H. Leon Bradlow, Ph.D., and Daniel W. Sepkovic, Ph.D., from Strang Cancer Research Laboratory in New York City; Andrea Micheli, Ph.D., Vittorio Krogh, M.D., and Franco Berrino, M.D., from the National Tumor Institute in Milan, Italy, and Martin Stanulla, M.D., from the Medical School of Hannover, Germany.

University at Buffalo

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.