It’s a cruel reality for breast cancer survivors: one-third of patients successfully treated for the most common kind of breast tumor will have their cancer come back after five or more years of treatment and after being declared cancer-free. While surgery, chemotherapy, radiation, and years of anti-estrogen therapy can knock-out the tumors—which contain estrogen receptors (ER+) and grow in the presence of estrogen—sleeper cells often remain. These cancerous cells are somehow able to dodge the treatments, survive in a patient’s body, and remain undetectable by standard clinical tests.
“If we can figure out how those cells survive and evade treatment, we can then look for drugs that will target them and prevent recurrence,” says Todd Miller, PhD, an assistant professor of pharmacology and toxicology at the Geisel School of Medicine, and scientific director of the Comprehensive Breast Program at Dartmouth’s Norris Cotton Cancer Center.
Thanks to a $100,000, two-year grant from the Mary Kay Foundation, Miller and Geisel graduate student Riley Hampsch are launching a study to identify the biological mechanisms that allow clinically dormant ER+ breast cancer cells to survive anti-estrogen therapy. But it won’t be easy.
“Clinical dormancy of these cells is not well understood because it’s not low-hanging fruit,” says Miller. “It’s hard and slow to study. You have to have a lot of faith that your experiment will work out because the time frame is so long.”
Simulating early-stage breast cancer treatment and then recurrence in mice takes several months, which is a relatively long time to wait for data in a study based on mice. The upside is that the study is relatively inexpensive and, ultimately, will yield important information. That combination makes it a great fit for a foundation grant, instead of larger, more restrictive National Institutes of Health grants, which have set milestones that must be met. After this pilot study, Miller anticipates applying for larger, longer-term grants to fund the next phase of the project.
“While great strides have been made in treating localized breast cancer, metastatic breast cancer is rarely cured,” Miller explains. “By the time recurrent cancers are discovered, they have often metastasized—spread to other organs.”
The hope is that Miller’s lab will reveal ways to kill or at least contain the dormant cells, thereby preventing them from proliferating and forming new tumors and, ultimately, turning deadly.