Can Breast Milk Serve as Breast Cancer Risk Indicator?

Newswise — AMHERST, Mass. – Early results of a study by researchers at the University of Massachusetts Amherst suggest that in the future, women and their physicians may have a new tool for evaluating breast cancer risk by examining epithelial cells naturally present in breast milk. The method could provide an earlier, personalized assessment of breast cancer risk than any of the currently available methods.

Environmental toxicologist Kathleen Arcaro of UMass Amherst is presenting preliminary findings of her nationwide study today at the American Association for Cancer Research 102nd Annual Meeting in Orlando, Fla.

Arcaro says that because about 80 percent of women give birth, non-invasively testing their breast milk for early indicators of elevated breast cancer risk would provide screening for a majority of women earlier than currently available and at a time (during pregnancy and lactation) when it is difficult to diagnose breast cancer. Other methods of obtaining breast cells to assess cancer risk in women of all ages exist, but techniques such as ductal lavage and nipple aspiration are invasive and yield very few cells, only tens or hundreds rather than the millions available from collecting breast milk.

For this study, Arcaro, associate professor of veterinary and animal sciences, and colleagues collected breast milk samples from both breasts from about 250 women nationwide who were scheduled for or who had already had a breast biopsy. About 90 percent of women who participated were recruited from the Love/Avon Army of Women.

The UMass Amherst team looked for evidence of an epigenetic response called methylation in three genes: RASSF1, GSTP1 and SFRP1 among the approximately 35 genes known to be methylated in breast cancer. Methylation silences gene expression, so tumor-suppressing proteins are not produced, which makes cancer more likely to occur. They chemically modified the DNA from epithelial cells from both breasts and used pyrosequencing to detect methylation in the promoter region of RASSF1, SFRP1 and GSTP1. The first two help in tumor suppression; the last makes a detoxification protein.

Early detection of methylation in breast tissue is a key in preventing cancer, Arcaro notes, and is the focus of a great deal of study. Epigenetic changes are not related to DNA mutations, and are often thought to be related to environmental exposures. They are passed on to dividing cells. However, methylation is reversible, so early detection increases treatment options.

Arcaro’s conference report this week is based on data from 182 women. In their first analysis, the researchers found a high methylation score in a small subset, the top 5 to 8 percent, of women with biopsies compared to a group of healthy women. Those with high methylation rates are of particular interest for further follow-up.

In a second analysis, she and colleagues assigned subjects to groups based on biopsy result: Non-proliferating disease, Benign proliferating disease, Proliferating lesions with atypia and Malignant lesions.

Arcaro and colleagues compared methylation levels in cells from biopsied vs non-biopsied breasts and observed greater methylation in the biopsied breast samples. “This methylation means that the helpful, tumor-suppressing genes are silenced, putting the woman at higher risk of developing breast cancer,” Arcaro explains. “This in itself is not enough, we need to look at a larger panel of genes. But to find these methylation differences between biopsied and non-biopsied breasts when we only looked at three genes is very interesting and encouraging. We’re seeing differences not related to lactation or pregnancy.”

“It clearly suggests that looking at a larger panel of genes would allow us to assess risk much more accurately, which leads to earlier detection of changes. A woman might be able to have her breast milk tested when she has a baby at age 25 or 30 and put her mind at ease, or give her an early warning.” Despite the small sample size, Arcaro says these data are “sufficient to tell us that methylation changes in breast cells may be detectable long before actual cancer development. So these changes may allow us to use cells in breast milk to assess breast cancer risk.” Because breast milk naturally flows from all the glands in the breast, Arcaro and colleagues’ new method surveys cells from all parts of the tissue, significantly extending the risk assessment reach to many more breast tissues than other methods.

Examining breast milk could show signs of elevated breast cancer risk in women at an earlier age than ever before, in a population currently not receiving mammograms or other screening.

More studies are needed to expand the number of genes, and long-term studies are now underway with about 80 percent of the original participants enrolled in long-term follow-up, Arcaro points out. She hopes that someday any woman who delivers a baby in a hospital could be screened for breast cancer risk via breast milk. “We’ll take a little sample of colostrum, and with a totally noninvasive and accurate assay, be able to tell her how her breasts are doing.” Women at elevated risk can then choose more frequent screening (mammograms) or potentially, new treatment options including demethylating drugs, which are far less drastic than, for example, mastectomy.

The UMass Amherst study is funded by the Congressionally Directed Medical Research Program and the Avon Foundation. The American Association for Cancer Research, founded in 1907, aims to prevent and cure cancer.