Author ORCID Identifier

https://orcid.org/0000-0001-5220-162X

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).

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