Table 1 Model parameters perturbed in the global sensitivity analysis.

Parameter	Symbol	Units	Baseline [range]	Distribution	Reference
Discrete (ABM) parameters
Cell cycle time*^,§	τ_P	hours	20 [16.5 – 23.5]	Uniform	[29, 30]
Symmetric proliferation probability
-progenitor (is daughter progenitor or differentiated?)*^,†,§§	ω_P	%	75% [50% – 100%]	Uniform	N/A
-stem (is daughter stem?)*^,†,§	ω_SC	%	12% [12% ± 6%]	Lognormal	[46]
-stem (are non-stem daughters ER + or ER–?)*^,§§	ω_SC,+/–	%	50% [36 – 64%]	Uniform	N/A
Apoptosis probability*^,§	ω_Apop	% Δt⁻¹	0.705% [0.10% – 1.31%]	Uniform	[47]
Proliferation cycles before differentiation*^,†,§§	P_max	Cell cycles	18 [11 – 25]	Uniform
Cell density threshold for quiescence*^,†,§§	θ_Q	Cells volume⁻¹	70% [50 – 90%]	Uniform	N/A
Dedifferentiation probability^†,§	Ω_DD	% cell⁻¹ cycle⁻¹	0.4% [0.1 – 0.7%]	Uniform	[24]
Hybrid (ABM ↔ continuum) parameters
Cancer cell oxygen metabolism multiplier (cancer cell oxygen metabolism = λ_C×λ_E)*^{,†, §}	λ_C	Mol cell^-1 s⁻¹	4.5× healthy cell metabolism [3.0 – 6.0×]	Uniform	[48]
Estrogen metabolism*^,§§	λ_E	Normalized (% baseline)	1.0 [0.9 – 1.1]	Uniform	N/A
FGF uptake/metabolism*^,§§	λ_FGF	Normalized (% baseline)	0.72 [0.648 – 0.792]	Uniform	N/A
AREG production*^,§§	λ_AREG	Normalized (% baseline)	0.086 [0.0774 – 0.096]	Uniform	N/A
Estrogen proliferation threshold*^,†,§§	θ_E	Normalized (% baseline)	0.85 [0.85 ± 0.2]	Lognormal	N/A
FGF proliferation threshold*^,†,§§	θ_FGF	Normalized (% baseline)	0.7 [0.7 ± 0.15]	Lognormal	N/A

Parameters were tested with either a uniform range [min-max] or a lognormally distributed range [mean ± error factor], with each run under a unique parameter setting determined by LHS. *Parameters perturbed in the full global sensitivity analysis without dedifferentiation. ^†Parameters perturbed in the dedifferentiation sensitivity analysis. ^§Parameters quantified from in vivo or in vitro experimental measurements. ^§§Parameters estimated mathematically or obtained from other modeling work.

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