Our experiments herein show that overexpression of histone deacetylases (HDACs) in breast cancer cell lines and clinical tumor specimens blunts PPARγ-mediated effector cascades and identify a rational pairing of HDAC inhibitors and thiazolidinediones which yields synergistic tumor-suppressive and anti-angiogenic effects against a range of triple-negative and ER-positive breast cancer models. The gene discussed is PPARG; the disease is breast carcinoma.