Study: genetics a factor in breast-cancer predictor

by Kelly Wittman

University researchers at the Minnesota Cancer Center have found a genetic link to the second strongest predictor of whether a woman will develop breast cancer.
The study, which will be published in today’s edition of the Journal of the National Cancer Institute, found that mammographic breast density is influenced by genetics, most likely by a dominant gene. Mammographic breast density is a measure of the concentration of mammary ducts, connective tissue and fat within the breast.
“We found that there is a familial tendency for some women to have a higher breast density,” said Thomas Sellers, lead investigator for the Breast Cancer Family Cohort study and associate director of the cancer center.
Women with higher breast density face a six times greater risk of developing breast cancer than women with lower breast density, Sellers said. The added risk of breast cancer to women with higher breast density is second only to the risk of breast cancer in women who have mutations of the BRCA1 and BRCA2 genes, he said. Women with mutations on these chromosomal areas have 50 times greater risk of developing breast cancer than women who do not have the mutations, Sellers said.
The discovery of the genetic link to breast density and cancer contribute to researchers’ understanding of breast cancer, which will eventually result in ways to prevent the disease, Sellers said. “We are trying to understand the causes of breast cancer in order to prevent it,” he said.
If 1,000 women’s mammographies were looked at by a radiologist, and the breast density measurements charted, the distribution of breast density in women would follow a regular curve with an average density of about 30 percent, Sellers said.
But Sellers and his co-researchers found that there is a subset of women, about 12 percent of the larger group, that have an average breast density of about 55 percent.
The genetic alteration that causes this higher density level appears to be a dominant trait, which means that women only have to inherit one copy of the gene to have increased breast density, and conversely, a higher cancer risk.
Sellers added, however, that his study did not completely rule out that the genetic component could be a recessive trait, and women would have to receive two copies of the gene to have higher breast density.
“Dominance appears to be a better fit, but we can’t rule out a recessive trait,” he said.
The study involved 1,370 women older than 40 who were asked to have a mammogram as well as answer questions about other health issues that might have affected their breast density.
Taking hormone replacement therapy, and such habits as smoking and drinking alcohol all increase breast density, Sellers said. Once the researchers controlled all of the environmental factors that could account for differences in breast density between the women in the study, a genetic pattern became clear, he said.
A unique thing about this study was that its methodology isolated factors like smoking and drinking that could account for changes in the women’s breast density and allowed researchers to find the genetic link, Sellers said. “We wouldn’t have had the results without the environmental risk factor data collection.”
The women who were sought to take part in the study were all relatives of 544 women who were breast cancer patients at the University between 1944 and 1952. Sellers said that the findings of his study were made possible by the earlier study of those 544 women done by Professor V. Elving Anderson, a co-author of the current study with Sellers.
Anderson said a major problem with a number of scientific studies is that they take time, which is especially true of studies in genetics that cross generations. When he did his original study of the 544 women, their daughters were young. The present study has taken the opportunity to go back and see what happened with those families, he said.
He also said the findings might not have immediate practical applications.”We have further work before we make that step,” he said.