Silicone Implant Shells Do Not Increase Proliferation Rate Of Triple Negative Breast Cancer Cells In An Engineered Biomimetic Patient-derived Breast Tissue
Ishani D. Premaratne, BA, Matthew A. Wright, BA, Mariam Gadjiko, BA, Danilo Fiore, PhD, Giorgio Inghirami, MD, Kristy A. Brown, MD, Jason A. Spector, MD.
Weill Cornell Medicine, New York, NY, USA.
PURPOSE: Breast implant safety has been called into question with recent concerns regarding Breast Implant Illness and possible links to cancer. However, limitations of current 2D models to study cell behavior in vitro make it difficult to accurately analyze how silicone implant shells may modulate the behavior of cancer cells. Our group has developed a novel 3D biomimetic platform which allows us to accurately recapitulate the breast cancer microenvironment in vitro, thus allowing us to map and quantify this cell behavior. Herein we present a study of the behavior of triple negative breast cancer (TNBC) cells in this biomimetic model, towards answering the many remaining questions regarding breast implant safety in the setting of cancer.
METHODS: Patient-derived breast tissue was processed for its component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 Ál of 0.3% type I collagen matrix with TNBC-468 cells at a density of 200,000 cells/mL before being plated into 6mm wells (the "biomimetic platform" groups). As a control, TNBC-468 cells were suspended within type I collagen at the same seeding density without breast components ("collagen only" groups). Before plating, wells were lined circumferentially with either textured, smooth, or no implant shell. These 1cm by 2cm pieces were dissected from the whole implant, autoclaved, and then placed in each well with the superficial aspect facing inward. Wells were imaged using confocal microscopy every other day over 10 days and then cell counts were quantified using ImarisTM software to study proliferation over time.
RESULTS: Over 10 days, TNBC-468 cell proliferation was significantly more robust in the biomimetic platform groups compared to the collagen-only groups regardless of implant shell type (p-value < 0.01). However, there was no statistically significant difference in TNBC-468 proliferation between smooth, textured, and no implant groups (Figure 1). Thus, while the presence of breast components did have an appreciable effect on cell proliferation, the presence of silicone within the well did not stimulate the cancer cells to proliferate at a faster rate.
CONCLUSION: Within a tissue-engineered three-dimensional ex vivo model of the breast microenvironment that incorporates different silicone shell types, we have demonstrated that TNBC-468 cells proliferate more robustly within the biomimetic platform when compared to collagen alone, but the presence or absence of implant shell had no significant effect on proliferation. Despite increased media attention surrounding breast implants and related safety concerns, our data provide further evidence that silicone breast implants alone do not stimulate breast cancer.
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