Accordingly, stERAP-2 and stERAP-6 possessed stabilized α-helices to specifically inhibit the interaction of BIG3-PHB2, thereby leading to E2-induced PHB2 suppressive activity, and karyopherin α-mediated nuclear-translocation of PHB217, resulting in the complete suppression of E2 signalling pathways in breast cancer by binding to nuclear ERα. The gene discussed is ESR1; the disease is breast cancer.