The primary objective is to determine the progression-free survival of lonafarnib in patients with locally advanced and metastatic breast cancer. The secondary objectives are to determine the clinical benefit response rate (CR+PR+SD > 180 day duration), determine overall response rate, and determine the toxicity profile of lonarfanib in this patient population. To be eligible for this study patients must have histological or cytological confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, must be able and willing to enroll in the companion study COE03, have measurable disease per RECIST, no evidence of CNS metastases, no history of Torsades de Pointes, ventricular tachycardia, ventricular fibrillation or ventricular flutter, and no prolonged QTC interval > 450msec on screening ECG. Registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator’s discretion.