  Breast cancer is one of the most challenging global health problems among
women. This study investigates the intricate breast tumor microenvironment
(TME) dynamics utilizing data from Mammary-specific Polyomavirus Middle T
Antigen Overexpression mouse models (MMTV-PyMT). It incorporates Endothelial
Cells (ECs), oxygen, and Vascular Endothelial Growth Factors (VEGF) to examine
the interplay of angiogenesis, hypoxia, VEGF, and the immune cells in cancer
progression. We introduce an approach to impute the immune cell fractions
within the TME using single-cell RNA-sequencing (scRNA-seq) data from MMTV-PyMT
mice. We further quantify our analysis by estimating cell counts using cell
size data and laboratory findings from existing literature. Parameter
estimation is carried out via a Hybrid Genetic Algorithm (HGA). Our simulations
reveal various TME behaviors, emphasizing the critical role of adipocytes,
angiogenesis, hypoxia, and oxygen transport in driving immune responses and
cancer progression. The global sensitivity analyses highlight potential
therapeutic intervention points, such as VEGFs' critical role in EC growth and
oxygen transportation and severe hypoxia's effect on the cancer and the total
number of cells. The VEGF-mediated production rate of ECs shows an essential
time-dependent impact, highlighting the importance of early intervention in
slowing cancer progression. These findings align with the observations from the
clinical trials demonstrating the efficacy of VEGF inhibitors and suggest a
timely intervention for better outcomes.
