Our previous study demonstrated the synthesis of compound 2-[1-piperonylpiperazin-1-yl]-3-chloro-1,4-naphthoquinone and its cytotoxic effects against lung, breast, prostate, and colon cancer cell lines (Deniz et al., 2015) (Figure  1).In light of this information, in this study we investigate the cytotoxic and apoptotic effects of the compound against two different breast cancer cell lines MCF-7 (ER+, PR+, HER2) and MDA-MB-231 (aggressive and triple-negative). This evidence concerns the gene ESR1 and breast carcinoma.