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Assessing promoter methylation patterns in breast milk may shed light on breast cancer risk
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AACR 102nd Annual Meeting
ORLANDO, Fla. — Biopsied breast milk had significantly higher methylation scores for one tumor suppressor gene and higher scores for another, according to findings presented here at the American Association for Cancer Research 102nd Annual Meeting.
Kathleen F. Arcaro, PhD, of the department of veterinary and animal sciences and the Social and Demographic Research Institute at the University of Massachusetts at Amherst, said multiple tumor suppressor genes are frequently methylated in the early stages of cancer.
“We wanted to see if examining methylation patterns in tissue before cancer is detected could allow accurate assessment of risk and aid in early detection,” Arcaro said. The researchers used DNA extracted from epithelial cells exfoliated in breast milk as the biomarker.
“Young women should be screened and know if they are at higher risk,” Arcaro said. “The potential implications of this approach are clear: Because methylation is potentially reversible with demethylating drugs, it may provide the impetus for developing regimens to reverse cancer-like methylation patterns.”
Results
Immunomagnetic separation was used to isolate epithelial-enriched cell fractions. Pyrosequencing was used to isolate DNA, which was bisulfite-treated for RASSF1, GSTP1 and SFRP1. “We have finished analysis for these three genes, and we plan on conducting this analysis for 12 genes,” Arcaro said.
The current findings are updated data from 250 women from 41 states. Complete biopsy reports were available for 182 women. Thirteen percent had cancers, and there were non-proliferative lesions in 138 women.
“Biopsied breasts had significantly higher overall mean methylation scores for the tumor suppressor gene RASSF1 and marginally higher mean methylation scores for the tumor suppressor gene SFRP1,” Arcaro said.
She said two different signals were evident in high-risk and low-risk breasts.
“When we limited the analysis to women who had cancer and just focused on a single gene, we saw that the biopsied breast was significantly more methylated than the unbiopsied breast,” she said. “In the breast biopsy population, the medians did not differ from the unselected population. However, outliers were higher than in the unselected population.”
Rationale
Arcaro said previous studies of this nature have been limited to cells obtained from fine needle aspirate, fine nipple aspirate and ductal lavage.
“These methods have several limitations,” she said. “Few cells are obtained; because the procedures are invasive, most women may not want to undergo them; also, they survey small area of the breast.”
In the current study, researchers gathered breast milk samples from both the biopsied and non-biopsied breasts of women scheduled for or who had undergone a breast biopsy. These samples were processed within 24 hours of expression.
“The population of this study was nursing and willing to give milk,” she said. “And because of their potential biopsy or biopsy status, they were at increased risk.”
Arcaro said results of this study could give premenopausal women the opportunity to determine whether they are at increased risk for breast cancer. If needed, they can initiate established screening methods, including mammogram.
“These results may also aid in detection of pregnancy-associated breast cancer,” she said. “Given the high percentage of women that give birth and therefore produce milk, if even for just a few days, a breast cancer risk screen based on epithelial cells in milk has the potential to affect a significant portion of all women.”
Arcaro said long-term follow-up is ongoing for women enrolled in this study to determine breast health outcomes, and that specificity and sensitivity data were not yet available.
Dr. Arcaro reports no financial disclosures.
For more information:
- Arcaro KF. #LB-443. Presented at: AACR 102nd Annual Meeting; April 2-6, 2011; Orlando, Fla.
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