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

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).

Available for download on Tuesday, May 17, 2022

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