In the present study, two derivatives of mito-fisetin (mF3 andmF7) were synthesized and tested against four cellular models of estrogenreceptor (ER)-positive breast cancer in vitro, namely, HCC1500, CAMA-1,HCC1428, and ZR-75-30 cells in proliferating and nonproliferatingstates, upon induction of senescence program by stimulation with theER-targeting drug tamoxifen. This evidence concerns the gene ESR1 and breast cancer.