Genetic clues may show which women face breast cancer risk from HRT

September 12, 2003

A genetic clue may eventually help physicians identify certain women who would face an increased risk of breast cancer from using hormone replacement therapy, according to researchers from the Keck School of Medicine of the University of Southern California.

Keck School scientists obtained mammograms on more than 200 women and found that those with a genetic variant developed denser breast tissue after using estrogen and progestin therapy than women without the variant.

Mammographic density is a risk factor for breast cancer and has been proposed as a marker for breast cancer risk.

"Our research is promising. We already know that only some women who use hormone replacement therapy with estrogen and progestin go on to develop breast cancer," says Giske Ursin, M.D., Ph.D., associate professor of preventive medicine at the Keck School and one of the study authors. "If we could have a way of picking out the subset of women who are at risk for breast cancer from using standard hormone replacement therapy, we could offer these women some other treatment for their postmenopausal complaints."

The researchers presented their findings at a meeting called "SNPs, Haplotype, and Cancer: Application in Molecular Epidemiology," sponsored by the American Association for Cancer Research. SNPs is scientific shorthand for single nucleotide polymorphisms, which refer to differences in specific genes within the human genome.

Researchers explain that 99.9 percent of the genome is identical in all humans. But the rest of the genome is where it gets interesting--and where SNPs can be found. These polymorphisms are bits of the genetic blueprint that exist in different varieties within the population. They may account for characteristics as obvious as hair color or as complicated as the body's ability to break down hormones.

In their study, Keck School researchers aimed to find out which polymorphisms might link female hormones to increased breast density. They obtained mammograms and DNA from 233 postmenopausal women ages 45-75 who were randomly assigned to take either estrogen-and-progestin therapy, estrogen-only therapy or a placebo.

Scientists checked each participant's DNA for the presence of five genetic polymorphisms associated with progesterone action or the body's ability to break down estrogen or progesterone. Because of the way genes are inherited from both parents, each participant could either have two copies of the polymorphism, one copy or no copies.

When researchers took women's mammograms after 12 months on the trial and compared them to mammograms taken at baseline, they saw something striking. They found that among women on estrogen-and-progestin therapy, those with either one or two copies of a polymorphism in one of the genes that break down progesterone had a substantially greater increase in breast density than women who had no copies of that polymorphism.

The bodies of women with this genetic variant may not be able to break down progesterone as well as those without the polymorphism, researchers theorize. They did not see the same effects in women using estrogen-alone therapy.

Among study participants as a whole, those on estrogen-and-progestin therapy saw their breast tissue grow 7 percent denser, while those taking estrogen alone had somewhat less of an increase in breast density. Women on placebo had no increase in breast density.

We do not yet know whether an increase in breast density translates into an increase in breast cancer risk. However, breast density may be a measure of breast cell multiplication. Researchers believe the more breast cells multiply over a lifetime, the greater the breast cancer risk. The estrogen and progesterone naturally present in young women cause breast cells to multiply, but as a woman enters menopause, hormone levels plummet and breast cell multiplication slows.

Hormone replacement therapy in postmenopausal women introduces hormones present in very small amounts in such women. That means additional breast cell multiplication--and potentially greater breast cancer risk.
-end-
Additional Contacts:
John Weiner
USC
323-442-2830

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.