In this study, we have shown that (i) TWEAK receptor was expressed in about half of human breast cancers, (ii) the anti-TweakR antibody PDL192 was efficacious in 4 of 9 TweakR-positive patient-derived breast cancer xenografts, and (iii) a predictive eight gene signature of response was defined from responding and resistant PDXs that could be applied to a large cohort of breast cancer patients. The gene discussed is TNFRSF12A; the disease is breast cancer.