Fig. 5
From: Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy
Evolutionary paths to different treatment outcomes. a Schematics of and example paths to the four defined treatment outcomes. In each simulation, the tumor grew to 10 billion cells and then was treated for 150 days. The size of the tumor and the first four resistant clones (R1–R4) are shown throughout primary tumor growth and treatment. b Stacked bar plots showing the proportion of simulated tumors with each of the four defined treatment outcomes for three plausible death rates of sensitive cells during treatment (d’ = 0.16, 0.2, or 0.25) and varying effective resistance aberration rates (μ, varied from 10−10 to 10−2 across the x-axis of each plot). The effective resistance aberration rate is the product of the rate of accumulation of genomic aberrations per site per cell division and the number of such aberrations that can confer resistance. Clonal replacement (blue) occurs at a rate of ~10% across many sets of parameters. c Inference of effective resistance aberration rates (μ) for tumors that shrink to 10–50% of initial tumor size with treatment (matching the degree of tumor shrinkage observed in our cohort). We show inferred μ for the three plausible sensitive cell death rates (d’ = 0.16, 0.2, or 0.25) and for possible treatment outcomes (clonal replacement, polyclonal resistance, and sensitive residual disease). For such large residual tumors to occur, either the sensitive cell death rate (d’) must be low, in which case clonal replacement cannot occur, or the effective resistance aberration rate (μ) must be high. Source data for panels b and c are provided as a Source Data file
