In summary, ESR1/BCL-2 and ESR1/ERBB2/EGFR groups of proteins are critically involved in survival and proliferation of MCF-7 and 4T1 breast cancer cells, and CA-based nanoformulations of the siRNAs targeting mRNA transcripts of each of the protein groups led to significant inhibition in tumor growth in a 4T1-induced syngeneic mouse model, thus suggesting their potential implications in therapeutic intervention of breast cancer. Here, ESR1 is linked to breast carcinoma.