University of Pittsburgh researchers at UPMC Hillman Cancer Center are working to better understand breast cancer to help with the diagnosis, treatment, and prevention of the disease. For example, they are examining the effects of hormones such as estrogen on breast cancer development and treatment; the different subtypes of breast cancer, including invasive lobular carcinoma and ductal carcinoma in situ; the effects of different stressors on breast cancer; genetic abnormalities in breast cancer; breast cancer metastasis; and discovery of novel drug targets – all to improve outcomes for breast cancer patients.
We sat down with three of our experts to understand the impact of breast cancer research and here is what they had to say.
What are some of the biggest contributions from UPMC Hillman to the larger field of breast cancer research?
Every researcher has a different approach, even within the same disease type. Using a systems biology approach, Dr. Zervantonakis has “uncovered how new therapeutic targets can be identified by understanding the response of the tumor ecosystem (both tumor cells and normal cells).”
While Dr. Zervantonakis focuses on putting the pieces of the system together to understand a larger picture, Dr. Oesterreich’s focus is on a specific subset of breast cancer. “We are world leaders in characterizing invasive lobular breast cancer (ILC) as a unique and independent disease. As a testament, we offered the first clinical trial exclusively for patients with ILC,” says Dr. Oesterreich.
How has breast cancer research as a field, generally transformed what we know about prevention, diagnosis, and treatment/care of breast cancer?
As a leader in the field of precision medicine, Dr. Lee has seen large steps forward in breast cancer care through “improved imaging for screening and detection of early disease and personalized surgery and treatment that leads to reduced toxicities and better outcomes.”
Dr. Oesterreich’s work builds upon precision medicine for specific disease types. “We have seen tremendous progress,” says Dr. Oesterreich. “For example, deep understanding of inter- and intra-tumor heterogeneity has enabled precision medicine, liquid biopsy can be used to monitor disease and treatment efficacy, new novel treatments have been enabled with high efficacy especially for estrogen receptor positive and HER2+ disease, and improved understanding of the role of exercise and body weight is improving breast cancer outcomes.”
How has your research impacted what we know about prevention, diagnosis, and treatment/care of breast cancer?
Dr. Zervantonakis has developed computational approaches to study how fibroblasts, a normal cell type responsible for producing the extracellular matrix in all mammalian tissues, impact sensitivity to HER2-targeted therapy. “We’ve demonstrated that HER2-therapy resistant BC cells can be eliminated by blocking the pro-survival signaling pathway MTOR, independent of genetic background,” says Dr. Zervantonakis.
Dr. Oesterreich’s research has shown that invasive lobular (ILC) breast cancer is a unique disease with biological and clinical differences compared to invasive ductal cancer. She notes that “ILC requires distinct management and additional research so that precision medicine can be applied.”
Dr. Lee has shown how breast cancer metastases evolve at the gnomic and transcriptomic level. “These changes often introduce new therapeutic vulnerabilities that can be used to better target the cancer,” he says.
What additional research is needed to drive innovations in the prevention, diagnosis, and treatment/care of breast cancer?
While artificial intelligence has been increasingly used for scientific discoveries, Dr. Oesterreich recognizes that it is necessary to continue moving the field forward. “To drive innovations in breast cancer we need increased use of AI to improve diagnosis of heterogenous breast cancer subtypes, better models that more accurately represent the different breast cancer subtypes, improved technology to use all components of liquid biopsies, and better understanding of the tumor microenvironment,” she says.
Dr. Zervantonakis builds on this approach acknowledging that new integrated computational-microfluidic approaches that study the heterogeneity of the tumor ecosystem will uncover biomarkers to guide therapy personalization. He notes that “it is necessary to develop new experimental model systems using cells directly from patient samples to establish more effective therapies, such as combination therapies that capitalize on FDA-approved drugs for other cancer types or new promising drugs.”
One way in which our researchers are using patient samples is through the Hope for OTHERS program, a collaboration between the University of Pittsburgh, UPMC Hillman Cancer Center, and UPMC Magee-Womens Hospital, that has allowed researchers to discover new characteristics of tumors through donation.
“We are incredibly grateful when patients with metastatic breast cancer donate their bodies at the end of life to research,” says Dr. Lee. “This has helped us to characterize metastatic disease better.”
About Our Experts
Ioannis Zervantonakis, PhD, is assistant professor in the Department of Bioengineering at the University of Pittsburgh and a member of the Cancer Biology Program at UPMC Hillman Cancer Center. His research interests include systems biology approaches to cancer drug resistance and metastasis in breast and ovarian cancer and understanding how the composition of tumors and their environments are impacted by drugs.
Steffi Oesterreich, PhD, is the Shear Family Foundation Chair in Breast Cancer Research and professor of pharmacology at the University of Pittsburgh. She is co-leader of UPMC Hillman Cancer Center’s Cancer Biology Program of and co-director of the Women’s Cancer Research Center, a collaboration between the UPMC Hillman Cancer Center and Magee Womens Research Institute. Her research focuses on better understanding how to most effectively treat breast cancers, including invasive lobular carcinoma (ILC) and estrogen receptor-positive (ESR1) breast cancer resistant to hormonal therapies.
Adrian Lee, PhD, is professor of pharmacology and chemical biology and human genetics at the University of Pittsburgh and a member of the Cancer Biology Program at UPMC Hillman Cancer Center. He is also the Pittsburgh Foundation Chair and Director of the Institute for Precision Medicine (IPM), a joint effort by the University of Pittsburgh and UPMC to move biomedical research into personalized well-being and clinical care. Using a systems biology approach, his research studies the molecular basis of breast cancer development and resistance to therapy, with the goal to identify and validate new drivers and therapeutic targets to improve precision medicine.