Surprisingly we found that expression of NRIF3 rapidly leads to caspase-2-dependent apoptosis in a wide variety of Estrogen Receptor positive or negative human breast cancer cell lines (e.g. SKBR3, MCF-7, T-47D, MDA-435, MDA-231 and MDA-231/ER+) and two mouse breast cancer cell lines (4T1 and 67NR) [2–5]. The gene discussed is ESR1; the disease is breast cancer.