To explore multitargeting in the context of combination therapy for the treatment of breast cancer, we investigated the enhanced growth inhibition of an investigational TKI, a 4,6-disubstituted pyrimidine EGFR inhibitor (EGFRi) [34], in combination with doxorubicin (Dox), a DNA damaging anticancer agent, in an ER+ breast cancer cell line, MCF-7, and a TNBC cell line, MDA-MB-231. This evidence concerns the gene EGFR and breast carcinoma.