Priscilla Furth: Testing Gene Variation Could Predict Breast Cancer Risk
Breast cancer researchers at the Georgetown Lombardi Comprehensive Cancer Center are imagining the day when mammography is used only on women with a higher certainty of developing a breast tumor. As it is now, every woman, starting in midlife, is counseled to receive mammograms over and over again, even though only a small minority in women (1 in 8 at most) will eventually develop the disease.
The goal the scientists are trying to reach is to develop a panel of tests that will accurately determine an individual woman’s future risk of developing breast cancer, so that those women at peril could be counseled and monitored. These tests would include specific behavioral and environmental exposure questionnaires, and, perhaps, a tiny bit of breast tissue that can unlock molecular secrets.
While others at the cancer center are researching the behavioral/environmental aspects of breast cancer risk, Priscilla Furth, MD, professor in the Department of Oncology, is working on what she says is the “heretical suggestion” that examining genes and proteins in “normal” breast tissue can help predict risk of future breast cancer.
“I think it will be possible to take a random sample of breast tissue and actually stratify people for future breast cancer risk,” says Furth. “A simple, small biopsy in younger women could tell us who needs to have frequent mammograms in the future, and who likely does not. This is the essence of individualized medical care and of disease prevention.”
Furth is uniquely situated to make this claim. She has developed mouse models in which she can manipulate various genetic factors to see how breast cancer risk changes over time. No one else has these tools, she says.
For example, she has explored the role of estrogen in breast cancer. “All women have estrogen, and estrogen is the major factor that drives breast cancer development – so why does estrogen appear to be an issue in only some women?”
To find out, she manipulated two genes in her experimental mice – one that codes for a protein receptor that binds to estrogen, and the other that regulates aromatase, an enzyme responsible for the synthesis of estrogen. Her changes in expression of these genes were very subtle, “meant to mirror the natural variation that we see in women.”
She found that over-expression of one or both of these genes measurably increased breast cancer risk in the mice. She has also examined levels of proteins she found promote cancer risk, and how they interact with estrogen receptors and other genes that are often variable in women. For example, a recent paper (Feb 24 online edition of Carcinogenesis) from Anne Miermont, who completed her PhD in Dr. Furth's lab, identified Stat5a as a protein factor that can modify the risk of development of both estrogen receptor positive and negative preneoplasia and cancers.
“We already could put a candidate gene test together but we want to hone it with further research,” Furth says. “We know how certain genes and proteins increase breast cancer risk in women, and we also know that levels of these same molecules are not the same across women.”
Gene and protein tests now exist for women already diagnosed with breast cancer in order to predict how patients will fare with specific treatment, but a “normal breast” test like Furth’s would be unique. “I want to personalize the care of women,” she says. “I want to be able to tell someone whether or not the signature of molecules in their breast makes them more, or less, susceptible to breast cancer."
Furth hopes development of such a test could help women choose the screening strategy that best matches their own risk profile.
By Renee Twombly, GUMC Communications