Breast cancer diagnosis and treatment are complicated by the fact that most solid tumors are heterogeneous and composed of diverse populations of tumor cells, as well as stromal cells. Tumor heterogeneity challenges therapeutic approaches because different populations of tumor cells within a given tumor respond differently to a given therapy. For this reason, it is essential to understand the mechanisms by which specific populations of tumor cells respond to therapy so that effective combinatorial strategies can be developed that overcome the challenge of heterogeneity. Within this context, a major goal of this thesis is to understand how diverse populations of tumor cells in breast cancer respond to ferroptosis. Using single cell RNA sequencing, I found that a subpopulation of luminal tumor cells with high expression of GATA3 in a patient derived organoid, show selective resistance to ferroptosis. Investigation of mechanism involved revealed that GATA3 promotes ferroptosis resistance through the downregulation of integrin β1 and the consequent inactivation of a FAK-ROCK-YAP pathway that culminates in the repression of ACSL4, a lipid-modifying enzyme that is essential for ferroptosis. These findings imply a novel role for integrin β1 signaling in promoting ferroptosis sensitivity and highlight the role of intratumor heterogeneity in determining ferroptosis resistance. The second part of my thesis focuses on the role of integrins in manipulating transcriptional patterns in epithelial and mesenchymal cell types. In this work, I highlight opposing roles for YAP/TAZ in promoting transcription of the LAMC2 subunit of laminin 332 in epithelial cell types while repressing transcription in mesenchymal cell types. Further investigation of this mechanism revealed that ZEB1 represses transcription of LAMC2 in mesenchymal cell types. In epithelial cell types, however, integrin β4 promotes downregulation of ZEB1 through mir200 and this repression allows for YAP/TAZ mediated transcription of LAMC2. Finally, I demonstrate that this positive feedback loop, in which integrin β4 promotes expression of its ligand laminin332, promotes an epithelial differentiated ferroptosis resistant cell state. In summary, this thesis highlights the effects of tumor heterogeneity on the response to ferroptosis inhibitors and demonstrates the role that integrins have in influencing cell state and ferroptosis sensitivity.