Mammographic density is one of the strongest predictors of breast cancer risk: Researchers

American Association for Cancer ResearchApr 22 2010

Women who have a breast density of 75 percent or higher on a mammogram have a risk of breast cancer that is four to five times greater than that of women with little or no density, making mammographic breast density one of the strongest biomarkers of breast cancer risk.

At the American Association for Cancer Research 101st Annual Meeting 2010, held in Washington, D.C., April 17-21, researchers will present the latest data on mammographic density and breast cancer risk.

"These abstracts strengthen the observation that high breast density is associated with increased risk for breast cancer, and they strengthen the hypothesis that under some conditions, reducing breast density may be associated with reduced risk for breast cancer," said Carol J. Fabian, M.D., professor of medicine in the division of clinical oncology and director of the Breast Cancer Prevention Center at the University of Kansas Medical Center.

Mammographic density refers to the amount of white or radiodense area compared to the amount of grey or radiolucent area on a mammogram. The radiodense area is reflective of the amount of ductal and lobular epithelium, connective tissue and fluid in the breast. The radiolucent area is reflective of the amount of fat in the breast.

While increased breast density is a known risk factor for breast cancer, having a lower breast density doesn't necessarily mean a low risk of developing breast cancer, according to Fabian. Other risk factors are at play, and mammographic density is one tool to help determine a women's risk.

"The cancer research community is always looking for new methods to better define short-term risk to supplement the known risk factors for breast cancer like family history, genes associated with hereditary breast cancer, reproductive variables and age," said Fabian. "Modifiable risk biomarkers like mammographic density are increasingly being used in small early phase prevention trials to help us decide which interesting strategies should be carried further into very large Phase III studies with cancer incidence as an endpoint."

The AACR has highlighted the following abstracts on new research in mammographic density, which will be presented at the Annual Meeting:

Women who have a decrease in breast density over a six-year period may have a decreased risk of developing breast cancer compared with women whose breast density remained stable.

"A decrease in breast density appears to be associated with a lower breast cancer risk, and importantly, this result takes into account baseline breast density, as well as changes in BMI that occurred between mammographic assessments," said lead researcher Celine M. Vachon, Ph.D., associate professor of epidemiology in the College of Medicine at the Mayo Clinic, Rochester, Minn.

Vachon and colleagues evaluated whether changes in breast density over time are associated with breast cancer risk using data collected as part of the Mayo Mammography Health Study, which included 19,924 women who had a mammogram at the Mayo Clinic between 2003 and 2006. Participants had never had breast cancer and were more than 35 years old at time of the mammogram.

Study variables were derived from clinical databases as well as self-administered questionnaires completed by the participants. The researchers performed linkages to Mayo and state cancer registries to identify new breast cancer events.

To examine the association between change in density with breast cancer, longitudinal analyses were conducted on the 219 breast cancer cases and 1,900 cancer-free cases that represented a random sample of the entire cohort.

Breast density was obtained from the earliest available historical mammogram, and from the mammogram that was obtained at the time of enrollment using the Breast Imaging-Reporting and Data System (BI-RADS) - a quality assurance mammography tool designed to measure clinical density that, for breast composition categories, is classified as almost entirely fat, scattered density, heterogeneous density and extremely dense. The differences between the BI-RADS measures obtained from the two time periods were used to evaluate changes in density over time.

Results showed that cases were less likely to have experienced a reduction of one BI-RADS density category or more (37 percent vs. 38.6 percent) after their earliest mammogram.

"Women who experienced a reduction of at least one density category over the six years were at reduced risk of breast cancer (28 percent lower risk) compared to those whose density was unchanged," Vachon said. "And, women who increased by one or more BI-RADS categories over the time period had suggestion of increased risk."

Change in mammographic density may be a useful intermediate marker to explain the increased breast cancer risk among postmenopausal women using estrogen and progestin therapy (EPT), according to results of a case-control study conducted within the Women's Health Initiative (WHI) randomized trial of EPT.

Mammographic density is one of the strongest predictors of breast cancer risk.

"As breast density increases so does women's risk for breast cancer - we were able to predict this risk in our study population," said lead researcher Celia Byrne, Ph.D., assistant professor of oncology at the Lombardi Comprehensive Cancer Center at Georgetown University.

Using data from the WHI, Byrne and colleagues evaluated the baseline and one-year follow-up mammograms from 97 women who developed invasive breast cancer in the EPT group and 77 in the placebo group. They also evaluated mammograms from a random sample of 733 healthy controls from both the EPT and placebo groups.

Approximately half (57 percent) of the women in the placebo group had a decline in mammographic density compared with 16 percent of the women in the EPT group. Forty-seven percent of the placebo group had a modest increase compared with 85 percent in the estrogen EPT group.

Among the postmenopausal women randomized to EPT, risk of breast cancer risk increased 3.6-fold in 20 percent, with the greatest increase in mammographic density.

The researchers also found that baseline and change in mammographic density were significantly associated with breast cancer risk in the EPT group. Comparing breast density from the first and second mammogram, they could "predict" the women at increased risk of developing breast cancer.

Consistent with the original findings of the WHI, the researchers reported an association between EPT and breast cancer risk; there was a 24 percent increased risk, which was explained by the change in breast density, according to Byrne.

In addition to considering change in breast density among postmenopausal women taking EPT, "baseline breast density needs to be incorporated more in thinking about breast cancer risk," said Byrne. "We need to better understand patients who aren't on estrogen and progestin therapy and what makes some women's breast density decline and others stay high."

Measuring breast density by dual energy X-ray absorptiometry (DXA) may provide a low-radiation option to evaluate breast density for women who do not undergo mammography.

According to lead researcher Gertraud Maskarinec, M.D., Ph.D., it is important to study breast cancer risk in younger women and identify women for targeted prevention strategies early in life. However, evaluating breast cancer risk through use of mammography is known to have a level of radiation exposure that is not acceptable for younger women; therefore, other methods are needed to evaluate breast density.

"Our findings indicate there is agreement between breast density as determined by mammograms and the use of DXA," said Maskarinec, who is professor of epidemiology at the Cancer Research Center at the University of Hawaii, Honolulu.

DXA is widely used to evaluate bone density and total body composition. It is commonly available in medical care settings and is known to have low radiation exposure.

Maskarinec and colleagues conducted a cross-sectional study to compare breast density measured by DXA with mammographic density among 101 women aged 30 years and older with a normal mammogram. Participants completed questionnaires on demographic, reproductive and medical information, and then received DXA scans of both breasts.

Both DXA and mammographic measures showed high correlations between left and right breasts and common risk factors showed similar patterns for both measurements.

"We now know something about how DXA performs when used to measure breast density," said Maskarinec. "This is not practice-changing at the moment, but it does present the potential for future studies to elaborate on DXA's use as a new research tool in breast cancer prevention studies among adolescents and young women."