Squamous Expression in Breast Implant Capsules: Insights into the Pathogenesis of Breast Implant-Associated Squamous Cell Carcinoma.

Abstract

Breast implant-associated squamous cell carcinoma (BIA-SCC) has emerged as a rare but aggressive malignancy with a mortality rate of 25% at 1 year. Its pathogenesis remains uncharacterized. Breast implant capsules from women 18 to 80 years old were systematically sampled in six locations at a single institution. Samples were analyzed for squamous marker expression including p63, p40, and cytokeratin 5 (CK5) using PCR. Immunohistochemistry was used to assess presence of proteins and squamous metaplasia. 23 breast implant capsules were analyzed for squamous-related gene expression. Compared to those with implants in place for less than 10 years (n=11), the cohort with implants in place for more than 10 years (n=12) had 26.9 times higher CK5 expression (p=0.02), 39.8 times higher p40 expression (p=0.001), and 54.2 times higher p63 expression (p<0.001). After adjusting for implant duration, there were no differences in squamous-related gene expression regarding implant type or texture or the presence of capsular contracture or implant rupture. Samples directly under pectoralis had 20.2 times higher CK5 expression (p=0.02), 45.9 times higher p40 expression (p=0.002), and 12.7 times higher p63 expression (p=0.04) compared to samples directly under breast or skin. These findings support a chronic inflammatory pathogenesis similar to Marjolin ulcer. Our results challenge the previous theory that BIA-SCC arises from entrapped ductal epithelium. Instead, we propose that the epithelial cells originate from local capsule cells such as fibroblasts or macrophages that undergo metaplasia. We also propose that mechanical stress from muscular contraction may induce a chronic wound repair-like process.