Ductal carcinoma in situ (DCIS) simulation -- extended results

Ductal carcinoma in situ (DCIS) simulation -- extended results

Agent-based simulation of ductal carcinoma in situ (DCIS), a type of breast cancer that is constrained to growth in the breast duct lumen by a basement membrane. Shown here: a simulation of 45 days' growth in a 1.5 mm length of duct. 

The mechanical and population dynamic parameters have been calibrated to patient-specific immunohistochemistry and other histologic measurements. 

Dark circles: cell nuclei
Green cells: proliferating cells (Ki-67 positive; S, G2, M, or G1)
Red cells: apoptosis cells (cleaved Caspase-3 positive)
Pale blue cells: quiescent cells (G0)
Dark grey cells: necrotic cells prior to lysis
Debris in centre of duct: necrotic cellular debris
Red dots in centre of duct: clinically-detectable microcalcifications

Method: Agent-based, lattice-free model. Cell velocities determined by balance of adhesive and repulsive forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes.   Results: First-of-its-kind calibration to patient pathology.  Model quantitative predictions that we validate against the clinical literature, such as:    Linear growth in ducts due to necrotic core biomechanics -- agreement with mammography literature   Growth rates 7.5 mm/year to 10.2 mm/year -- quantitative agreeement with clinical literature   Linear correlation between mammography size and pathology size -- quantitative agreement with 87 patient measurements spanning two orders of magnitude in clinical literature   Age-structured, layered necrotic core microstructure -- agreement with patient pathology    Tear at perinecrotic boundary due to necrotic cell biomechanics (first explanation for the "artifacts" in DCIS pathology) -- agreement with patient pathology   New predictions of long-time necrotic core and microcalcification evolution -- agreement with mammography and biochemistry literature   Source: Macklin et al. 2011 in review.