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Breast cancer is a heterogeneous disease and remains as a leading cause of cancer-related deaths among women worldwide \cite{kashyap2022retracted}. Estrogen receptor-positive(ER+) breast cancer accounts for approximately 70\% of all diagnosed cases \cite{hanker2020overcoming}. The tumor microenvironment (TME) plays a pivotal role in modulating cancer progression and mediating therapeutic resistance. Cancer-associated fibroblasts(CAFs) are major constituents of the tumor microenvironment and they have different phenotypic subtypes \cite{chen2019turning}. Experimental evidence suggests that CAFs can facilitate estrogen-independent tumor growth, thereby undermining the effectiveness of endocrine therapies\cite{reid2024cancer}. We construct a mathematical framework based on a system of nonlinear ordinary differential equations to investigate the influence of CAFs on ER+ breast cancer progression and estrogen-independent growth dynamics. We fit the model to mice experiments \cite{reid2024cancer}. Then, we implemented three different treatment strategies as an optimization problem to reduce tumor size during treatment. Taken together, our results suggest that incorporating CAF-targeted strategies may enhances treatment efficacy across various estrogen dosing regimens and CAFs could be a therapeutic target to avoid drug resistance.
Bibliography
\bibitem{chen2019turning}
Xueman Chen and Erwei Song.
\newblock Turning foes to friends: targeting cancer-associated fibroblasts.
\newblock {\em Nature reviews Drug discovery}, 18(2):99--115, 2019.
\bibitem{hanker2020overcoming}
Ariella~B Hanker, Dhivya~R Sudhan, and Carlos~L Arteaga.
\newblock Overcoming endocrine resistance in breast cancer.
\newblock {\em Cancer cell}, 37(4):496--513, 2020.
\bibitem{kashyap2022retracted}
Dharambir Kashyap, Deeksha Pal, Riya Sharma, Vivek~Kumar Garg, Neelam Goel, Deepika Koundal, Atef Zaguia, Shubham Koundal, and Assaye Belay.
\newblock Global increase in breast cancer incidence: risk factors and preventive measures.
\newblock {\em BioMed research international}, 2022(1):9605439, 2022.
\bibitem{reid2024cancer}
Steven~E Reid, Jessica Pantaleo, Paulina Bolivar, Matteo Bocci, Jonas Sj{\"o}lund, Mikkel Morsing, Eugenia Cordero, Sara Larsson, Maria Malmberg, Brinton Seashore-Ludlow, et~al.
\newblock Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.
\newblock {\em Oncogene}, 43(15):1113--1126, 2024.
