Where will her journey of discovery lead now?
On the therapeutic side, Dr. Polyak is talking with pharmaceutical companies about clinical testing of compounds to block overactive signaling from stromal cells. Ian Krop, MD, PhD, a physician-scientist in Polyak's lab, is interested in testing inhibitors of the cytokines that the gene survey found were overactively signaling cells in the breast epithelium.
In these images, round or oval shapes are cross sections of milk ducts filled with blue-stained cancer cells. Tissues surrounding the ducts—whitish areas with red dots— contain "stromal" cells that aren't cancerous, but harbor genes that cause cancer cells within ducts to become more aggressive.
Other research is looking at the activity of stromal cell genes in DCIS lesions that have a high risk of becoming invasive cancer, compared to lesions tending to remain harmless for many years.
If the scientists could discover a distinctive pattern of gene activity in the stromal cells that appears when DCIS is likely to progress, it would help clinicians and patients make decisions about how aggressively to treat the cancer. Dr. Polyak has proposed a study that would analyze tissue from 600 women whose DCIS was monitored for 10 years to observe which cases progressed to invasive breast cancer and which remained stable.
"We'd be looking for a gene expression signature that would predict their risk of progression," says Dr. Polyak. "Now, every patient with DCIS gets surgery and many get radiation: The question is whether that is really necessary in every case."
She's also pursuing experiments to literally reconstruct invasive breast cancers in mice. First, cells from a human DCIS lesion are transplanted into a mouse. Then the researchers inject human stromal cells "to see how it affects the structure and the progression of the tumor." The goal is to identify genes that are overactive, as well as to find targets to hit with specific drugs.
"It's a huge amount of data and a lot of work," Dr. Polyak says of the road ahead. "But since our paper was published, people have gotten in touch who are interested in collaborating with us. This is a very exciting time in this area of research."
