ERRα was predicted to bind to the serine hydroxymethyltransferase 2 (SHMT2) transcription initiation site in the ER- and HER2-positive cell line BT-474; thus, we hypothesize that ERRα might modulate the resistance of breast cancer to lapatinib via regulating SHMT2. The gene discussed is ESRRA; the disease is breast carcinoma.