Dr. Angela DeMichele on Team Science and Curing Breast Cancer Through "Many Small Steps"

Apr 11, 2023

Dr. DeMichele Will Receive the 2023 Gianni Bonadonna Breast Cancer Award

By Jasenka Piljac Zegarac, PhD

Several decades ago, Angela DeMichele, MD, MSCE, was admiring ASCO’s award honorees, hoping to someday make her own impact as a physician–scientist. This year, she is proudly following in their footsteps as the 2023 Gianni Bonadonna Breast Cancer Award recipient. Her award lecture is scheduled to take place during the ASCO Annual Meeting Opening Session on June 3.  
“I have to say that I am beyond honored to receive the award,” Dr. DeMichele said. “I was completely surprised to be selected... it’s an interesting thing when you’ve had a 25-year career, and look up to people receiving these awards, and hope that someday you can make a contribution that would be worthy of such an award. It is really such a humbling experience.” 
Dr. DeMichele is a professor of medicine and holds the Jill and Alan Miller Associate Professorship of Breast Cancer Excellence at the University of Pennsylvania Perelman School of Medicine, where she is also the co-leader of the Breast Cancer Research Program at Penn Medicine’s Abramson Cancer Center.  

Early Beginnings in Breast Cancer Research 

Dr. DeMichele is known for her instrumental role in the development of palbociclib, one of the first CDK4/6 inhibitors. She credits early fellowship mentors John H. Glick, MD, of the University of Pennsylvania Perelman School of Medicine, and Lynn M. Schuchter, MD, of Penn Medicine, for guiding her on the path to clinical research and helping her find her niche in breast cancer.
In addition, “Dr. Peter O’Dwyer, who’s now the group chair for ECOG-ACRIN [the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network], was instrumental in teaching me to be a clinical trialist and gave me opportunities to develop palbociclib, one of the first CDK4/6 inhibitors, as well as opportunities within ECOG-ACRIN,” she said. “Dr. Laura Esserman, a surgeon who leads the I-SPY Trial Consortium, was also a very early mentor and supporter who I happened to meet fortuitously because she was visiting Penn [Medicine] . . . when I was a second-year faculty member.”  
That chance meeting led to a 23-year collaboration and mentoring relationship, as well as training in the development of neoadjuvant therapy and new drugs in that setting. “I’ve learned so much from Laura and I’ve made so many contacts because she had faith in me and gave me responsibility,” she added. 
Another 20-year collaboration and partnership with basic scientist Lewis A. Chodosh, MD, PhD, chair of cancer biology at Penn Medicine, led to the founding of the 2-PREVENT Translational Center of Excellence in Breast Cancer at the University of Pennsylvania, which focuses on preventing, identifying, and treating minimal residual disease (MRD) and treatment side effects in patients with breast cancer. 

A Moment to Remember 

In reflecting on the important moments in her career, she highlighted the work on CDK4/6 inhibitors and the first patient treated with palbociclib.  
“I gave palbociclib to the very first patient with breast cancer in our phase 1 trial,” she said. “I did not know at the time that that would be such a landmark moment, but that patient responded to the drug for a year and a half, which was unheard of back then, and had very few side effects.” 
This unexpected finding opened her eyes to the potential that targeted agents and precision medicine can have in treating cancer. It also led to additional trials of palbociclib in the metastatic and adjuvant settings. 
“That was really a galvanizing moment for me,” she said. “I realized that I could both really change the trajectory of the disease for an individual patient while at the same time learning something that could benefit many, many patients beyond that individual.” 
“That’s really what we hope to do as clinical researchers,” she added. “Learn from our patients, be able to do research that clearly benefits them but also to take that knowledge to develop strategies and therapies that can benefit a much larger population than we could ever treat ourselves.” 

Eliminating MRD 

Her current work is focused on finding effective strategies for detecting and eradicating MRD after breast cancer treatment. She noted that, until now, the strategy has been to treat patients with upfront therapy, surgery, and adjuvant therapy and continue with watchful waiting, which can be incredibly distressing.  
“We have the opportunity now to change that paradigm, to utilize these new tools―circulating tumor DNA, disseminated tumor cells, and other emerging biomarkers―to measure MRD, to identify those patients who have it, to target it with the drugs that specifically eradicate it, and to monitor patients on an ongoing basis to make sure that they stay free of the cells that could lead to recurrence,” she said. “That is the missing piece we need to make sure that no one dies of breast cancer.” 
She further noted that this is especially relevant for patients with ER-positive breast cancer where recurrence happens beyond 5 years in at least 50% of the cases. “I am working on a large trial right now with a group of investigators across all of the cooperative groups where we will be actually enrolling patients at that point in time―3 to 4 years after diagnosis―looking for MRD, so that in those patients we can switch therapy if we find evidence of MRD. The trial is designed to determine whether we can head off recurrence because late recurrence is a huge problem in ER-positive breast cancer.”  

Mentoring the Next Generation of Cancer Researchers 

The Gianni Bonadonna Breast Cancer Award recognizes researchers who, in addition to making important contributions to the field of breast cancer, have served as exceptional mentors. Along those lines, Dr. DeMichele emphasized the joy that mentorship brings to her every day. 
“I think that mentoring is one of the most important things we do in our field,” she said. “I think it’s a 2-way street―as a mentee, you see someone who exemplifies what you hope to learn and achieve, and at the same time the mentor can see your potential and nurture it.” 
She believes that to be successful, mentees need to learn not only how to achieve research quality and integrity of the scientific process, but also to build personal resilience through close collegiate relationships and earn the trust of patients.  
“I hope that my mentees find balance in their work but also in their lives because it can be so challenging... we lose patients and have failures in the laboratory or in our research,” she said. “These things can be very discouraging. But if they are attending to their needs and taking care of themselves and their families, it’s much easier to weather these challenges.” 
During her lecture, she will discuss how her research experience has helped her develop approaches to solve big problems in breast cancer.  
“What I hope my talk will be able to do is to help junior people just getting started to see what my path was like—a ‘Team Science’ approach, full of good things, hard things, and the ups and downs of a research career,” she said. “I think that too often we’re focused on the big wins, but I believe that we are going to cure breast cancer in many small steps achieved through collaboration and teamwork.” 
“What you learn from the things that didn’t work,” she added, “can be more important than what you learn from the things that did.” 
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