Grants Funded

Abstract

Project Summary:
In the United States, there are currently 1 to 2 million estimated patients with breast implants (1). Several diseases associated with breast implants have been described in scientific literature and researched thoroughly such as breast implant illness (BII) and breast implant-associated anaplastic large cell carcinoma (BIA-ALCL). However, in the last decade, there have been several cases of breast implant-associated squamous cell carcinoma (BIA-SCC), which is a far less researched and more serious illness with significant morbidity and mortality (2-4). In comparison to BIA-ALCL, which has a lower than 5% mortality rate 1 year after diagnosis, over a quarter of patients with BIA-SCC will die within a year of diagnosis (4). In 2022, the FDA publicly announced that BIA-SCC is a risk of breast implants, which increased physician awareness and reporting (5). Following this announcement, there was a 50% increase in total cases of BIA-SCC in the US (6). Because of the aggressive nature of this cancer and the large number of patients with implants, it is imperative that BIA-SCC is researched. Currently, we do not understand the pathogenesis of this invasive disease nor do we have any method by which to screen patients.
We propose that squamous metaplasia is a precursor to BIA-SCC, which would be consistent with squamous cell carcinomas that arise from other chronic inflammatory responses, such as the cancerous Marjolin ulcer. In many cases of identified BIA-SCC, there is also squamous metaplasia present, which also suggests it could be a precursor (7-9). To investigate this, we will study breast implant capsules, which are normally created by the body's inflammatory system in response to the breast implant. We will look at the capsule on a cellular level through immunohistochemistry, utilizing stains that allow us to visualize squamous cells. Further, we will investigate the capsules on a subcellular level with flow cytometry and real time-polymerase chain reaction. This research will play a pivotal role in understanding the pathogenesis of BIA-SCC and creating data-driven guidelines on screening for BIA-SCC, which will prevent morbidity and mortality associated with this disease process.

Impact Statement:
While guidelines exist for the treatment of identified BIA-SCC, there are no surveillance methods in place to target a potential pathological precursor of BIA-SCC. If our hypothesis that squamous metaplasia is a precursor of BIA-SCC is true, we could create evidence-based guidelines for the management of patients with squamous metaplasia on pathology. This project will lay the groundwork for evaluating the cellular origin of BIA-SCC. Future projects can then aim to create animal models replicating the process of squamous metaplasia in the breast capsule so we can further understand which molecular signaling pathways are associated with the malignant transformation of squamous metaplasia to BIA-SCC, and thereby develop targeted interventions.

Biography
Dr. Megan Fracol is an Assistant Professor in the Division of Plastic and Reconstructive Surgery at Northwestern Memorial Hospital. She graduated AOA from the University of Pennsylvania Perelman School of Medicine, followed by a seven year residency in plastic and reconstructive Surgery at Northwestern Memorial Hospital. She then went on to complete a microsurgery fellowship at M.D. Andeson Cancer Center. Her research and clinical interests have always centered around breast reconstruction, with a particular niche in immune-mediated mechanisms of breast cancer prevention/treatment. She worked on an anti-HER-2 targeted breast cancer vaccine in medical school. In residency, she received over $250,000 in grant funding to study how the inflammatory response around the foreign body breast implant can create anti-tumor antibody responses to breast cancer antigen. In fellowship, she became one of the world experts on breast implant-associated malignancies and helped to develop consensus guidelines for management of breast implant-associated B cell lymphomas and squamous cell carcinoma.