Alexa Glencer

Why Was I interested in this T32?

I knew that I wanted to pursue a career in surgical oncology when I applied for the T32, but this particular T32 is unique in its structure. In addition to supporting surgical residents interested in performing translational research, it also encourages residents to become involved in regulatory and implementation science. The guest lecture series, reminiscent of a business school curriculum, introduces residents to leaders in the healthcare field beyond academia in a small-group context that is incredibly valuable.

What did I work on in my T32 research project?

My funded T32 work was clinical and translational research designed to enhance our understanding of the biology and tumor immune microenvironment of breast ductal carcinoma in situ (DCIS). I worked with a multi-institution and multidisciplinary group (including Dr Esserman, Dr Hirst, Dr Campbell) on a project termed DEFENSE, which is a study that uses molecular phenotyping, whole exome DNA sequencing, and multiplex immunohistochemistry to characterize large, high-risk DCIS lesions and their microenvironment. We found that DCIS lesions that were HER2+ or were hormone receptor negative were characterized by dense surrounding immune infiltrate, which is a pattern also seen in invasive breast cancer that is HER2 positive or triple negative. I have presented this work at multiple national meetings, most recently winning an award at the 2021 SABCS conference. 

I also used my research funding to evaluate a unique cohort of women with DCIS who elected to manage their disease with endocrine therapy and serial breast MRI rather than surgery unless there was evidence of invasive progression. With long follow-up (8 years), this study found that more than half of women with DCIS can safely avoid surgery. The resulting manuscript is currently under review at Clinical Cancer Research.

Finally, I have been involved in the analysis of results of a phase I study of intralesional pembrolizumab in women with high-risk DCIS; during my research period, we also modified the study protocol to add a second agent that encodes three cytokines intended to enhance the immune response generated by pembrolizumab in the local tumor immune microenvironment. Patients are actively being enrolled on this dual-agent regimen, and analysis is ongoing. The results of the phase I monotherapy study were published in npj Breast.

Important lessons I learned from the T32 program and the  I2I Leadership course

I have learned that generating effective change in the American healthcare system requires the buy-in of multiple stakeholders beyond the physicians running clinical trials. In order to partner effectively with industry, which often enhances the speed at which trials can be conducted, a short-term metric must be defined that will demonstrate effect and has the potential to be translated into a therapy that can be brought to market.