Models for implant-induced capsular contracture post breast cancer surgery

by Cheryl Dyck, Kathryn V. Isaac, and Leah Edelstein-Keshet

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Surgical breast reconstruction can play an important role in the emotional and psychological outlook of a breast cancer patient.  Unfortunately, a common complication of implant-based reconstruction is capsular contracture (CC), formation of a painful and often disfiguring scar-tissue around the implant. Treatment for CC generally requires surgical capsule excision and implant replacement.  CC etiology is poorly understood, limiting the ability for determining a patient's risk profile, treatment, and prevention. Here we examine the early stages of CC development with a hierarchy of mathematical models for interacting macrophages, fibroblasts, myofibroblasts, and collagen. A simplified "toy" model provides insight suggesting parameter regimes that lead to either a stable state with a non-pathological thin capsule, a stable state with a pathological thick capsule, and a bistable range in between.  A fold bifurcation can exist with the full model with outcome determined by genetic and health profile (parameter values) and inflammatory state (initial conditions.) These results predict some patients are resistant to CC, some are destined to have CC, whereas a susceptible population could develop CC as a result of inflammatory insult.  Further examination and clinical study of the parameters of interest may yield risk factors and preventative and therapeutic targets.

Cheryl Dyck MAsc (SFU) is a Mathematical Biology Consultant. Kathryn V. Isaac MD FRCSC MPh, is a Plastic and Reconstructive Surgeon with Vancouver Coastal Health and Providence Health Care, an Assistant Professor, Department of Surgery, Faculty of Medicine, University of British Columbia, Canada and P. Clugston Chair of Breast Reconstruction.  Dr. Edelstein-Keshet is a Professor in the Department of Mathematics, University of British Columbia, is the author of "Mathematical Models in Biology (2005) SIAM", and a former president of the Society for Mathematical Biology.

Caption: Schematic diagram for a model of the early phases of tissue recovery around a breast implant (capsule formation.) The implant surgery initiates an immune response that eventually recruits collagen-producing cells. The collagen affects tissue stiffness, and feeds back on the balance between fibroblasts and their activated phenotype, myofibroblasts, further influencing collagen production.  Model analysis and simulations predict whether patients are resistant, susceptible, or prone to developing capsular contracture, a painful and disfiguring deformation of the reconstructed breast. Scheme made with Biorender