Author ORCID Identifier
Date Available
5-17-2022
Year of Publication
2020
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Medicine
Department/School/Program
Behavioral Science
First Advisor
Dr. Timothy A. Butterfield
Second Advisor
Dr. Henry C. Vasconez
Abstract
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that can form around textured-surface breast implants. In this dissertation, the cellular and molecular mechanisms of BIA-ALCL are reviewed with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Herein, the epidemiology of BIA-ALCL is systematically studied to better define the risk of BIA-ALCL and to determine the oncologic safety of smooth surface devices relative to BIA-ALCL formation. Next, a systematic review is conducted which critically appraises current clinical guidelines in order to establish an evidence base to better inform diagnosis and treatment. Finally, a molecular investigation is undertaken to determine the biological mechanisms of the disease which revealed pervasive upregulation of the JAK-STAT3 pathway as a key pathogenic feature in BIA-ALCL tumorigenesis. Herein, a novel mechanism of tumorigenesis via the JAK-STAT3 pathway is proposed—highlighting its potential mechanistic role. Collectively, the clinical research studies that comprise this dissertation demonstrate the oncologic safety of smooth-devices while illustrating substantial knowledge gaps in the risk of BIA-ALCL for commercially available textured breast devices in the U.S. market. This work also provides evidence-based recommendations and updates on diagnosis and treatment. Finally, this dissertation shows that BIA-ALCL tumorigenesis likely occurs through a novel mechanism that facilitates malignant transformation from a chronic inflammatory state through the JAK-STAT3 pathway.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2020.174
Funding Information
Dr. DeCoster was supported by a surgeon-scientist grant from the National Cancer Institute (T32CA160003). This work was partially supported by a research grant from the Southeastern Society of Plastic and Reconstructive Surgeons (2018-2019).
Recommended Citation
DeCoster, Ryan, "BREAST IMPLANT-ASSOCIATED ANAPLASTIC LARGE CELL LYMPHOMA: MOLECULAR FEATURES, EPIDEMIOLOGICAL RISK FACTORS, AND EVIDENCE-BASED CLINICAL RECOMMENDATIONS" (2020). Theses and Dissertations--Clinical and Translational Science. 11.
https://uknowledge.uky.edu/cts_etds/11
