Working Toward the Cure
From preventive strategies to subtype identification and metastasis, UMass Amherst researchers have breast cancer research covered and are pioneering ways to address prevention and treatment of the disease.
Known for her ongoing 20-plus year stint as a senior investigator on the Nurses’ Health Study (NHS) I and II, two long-term ongoing cohort women’s health studies, Hankinson is no stranger to women’s health issues. Hankinson is currently investigating the associations between hormones and breast cancer. She has already helped establish that sex steroids and prolactin are breast cancer indicators in postmenopausal women, and is now fine-tuning that research to more accurately evaluate their contribution to individual risk prediction. “We’re now evaluating how much new information those hormone levels can add to what we already know about breast cancer risk factors,” says Hankinson, “in order to see if we can use that clinically to help women decide if they’re at high enough risk to be screened more frequently or potentially to use chemoprevention.”
Hankinson was also granted $1.8 million from the National Institutes of Health to research the role androgens, hormones that can be converted to estrogen in the breast, play in the development of the disease. If androgens are found to be important, existing or new anti-androgen therapies might provide an alternative prevention strategy for breast cancer, says Hankinson.
One of the unsolved mysteries of breast cancer, and another of Hankinson’s research interests, is why the relationship between body size and breast cancer changes throughout life. Overweight children and adolescents are at lower breast cancer risk as adults, while overweight postmenopausal women are at higher risk of breast cancer. Working with Jerry and colleagues at Baystate Medical Center, Hankinson aims to identify some of the underlying pathways responsible for the association.
“We know that obesity has a very complicated but a large impact on breast cancer risk and outcomes,” Jerry says.
The breast cancer patient registry that Jerry and his colleagues at the Pioneer Valley Life Sciences Institute (PVLSI) and Baystate Medical Center have generated contributes high-value patient information to many who are researching the disease, including Hankinson and Peyton. Jerry explains that the breast cancer awareness community has had a big impact on the registry—women who go to Baystate Medical Center for treatment and preventive care have rallied around the opportunity to help cure the disease. The registry provides a foundation from which factors embedded in the patients’ medical history that influence breast cancer can be more easily deciphered—information that is important to Hankinson as she maps the relationship between childhood obesity and the disease. Jerry, who studies the disease in animals, says the Institute provides a unique opportunity to draw parallels between what they learn in the laboratory with model systems to what is happening in humans.
Jerry, PVLSI Science Director, and oncologist Grace Makari-Judson were recently granted $1.5 million from Springfield’s Rays of Hope Foundation to further the Institute’s breast cancer research. By connecting academic researchers with clinicians, the Institute is developing unique and more personalized ways to treat the disease. The Institute’s breast cancer registry has grown rapidly and is an integral part of Jerry’s personal research. He explains that the registry allows him to look across the thousands of genes within the patient to develop a “signature.” Jerry is using gene expression profiling to investigate the ways the disease can manifest and is using the registry to identify high-risk subtypes of atypical hyperplasia, or pre-malignant breast lesions. He is looking for gene expression signatures that will enable clinicians to more quickly identify the 20 percent of women diagnosed with atypical hyperplasia who are likely to develop full-blown breast cancer, so they can be treated proactively.
Once preventive measures have failed, clinicians could benefit from knowing how the cancer will spread according to the various disease subtypes—an area Peyton is working on. Within recent years, the young researcher has received several large grants from the National Institutes of Health, the National Science Foundation and the Pew Charitable Trusts to further her research, which employs stem cells to mimic the various tissues breast cancer can spread, or metastasize, too.
Trained in biomaterials, Peyton uses stem cells to recreate the microenvironments the cancer cells would normally inhabit, while most researchers use a common glass plate. She explains that because the common model is inadequately human, many clinical trials have failed.
“We have these rich, complex microenvironments that cells live in,” Peyton says. “And so if we really want to understand what’s happening during the biology of disease, we have to put cells in their appropriate context.”
Peyton explains that there may be as many as 20 different subtypes of the disease, and all of those subtypes metastasize differently. Some spread only to bone, while others travel quickly to the brain and lung. It is of great value to clinicians to understand that relationship in order to identify areas to screen more frequently, as the screening is costly and resource-intensive. Using information from Jerry and the PVLSI registry, Peyton is mapping the different paths of metastasis according to the identified subtypes. This work is already yielding some predictive powers, which Peyton is working with graduate student Laura Barney to publish.
In addition to predicting risk of metastasis, Peyton aims to use her knowledge of that process to engineer a new type of drug to treat the disease. Most drugs used to treat breast cancer target the cancer cells themselves, but Peyton is paying close attention to healthy cells within the various tissues and what they do to help the tumor grow. A certain type of cell, called mesenchymal stem cells, is present in all human tissue in order to help regeneration in case of injury. Confused by the presence of cancer cells, these cells rally to help heal the area, deeming the cancerous tissue a wound. However, instead of helping, these cells catalyze the growth of the tumor. Peyton believes that by creating a drug that changes the behavior of the mesenchymal stem cells, cancer growth could be stopped.
Though she remains a ways away from clinical trials, Peyton hopes her more immediate results inspire others to use more realistic models to study breast cancer.
“What we really want to do is open up that field to the possibilities of studying cancer biology in these pretty easy to use and realistic microenvironments,” Peyton says.
Hankinson, Jerry, and Peyton are united around a common goal: to mitigate (and ultimately cure) breast cancer. Because they each have a piece of the puzzle, they have found it greatly beneficial to collaborate towards that end.
“There’s a tremendous amount that’s changed with breast cancer,” says Jerry. “Though there’s more work to do, we [the field] have made extraordinary leaps.”
Amanda Drane '12