Inclusion Criteria:

• Postmenopausal women who have histologically-confirmed breast cancer with the following characteristics:

  • estrogen and/or progesterone receptor positive,
  • locally advanced disease
  • distant metastatic disease, stage 4
• Subjects eligible for single-agent treatment with aromatase inhibitors for current disease.
• Subjects taking biophosphonates are allowed if they begin bisphosphonate therapy AT LEAST two weeks prior to randomization.
• Measurable disease (masses with clearly defined margins on radiological images and at least one diameter >=20 mm[>=10 mm if spiral CT]) or evaluable disease (masses with margins not clearly defined on radiological images or with no diameter >= 20 mm). Subjects with bone disease only are permitted if disease is evaluable.
• ECOG Performance Status of 0 or 1.
• Sufficient bone marrow reserve.
• Adequate hepatic and renal function: laboratory values within protocol requirements.

Exclusion Criteria:

• Subjects who have received more than one regimen of cytotoxic chemotherapy for advanced disease.
• Subjects with with CLINICALLY APPARENT brain metastases or extensive visceral disease, including extensive hepatic involvement or pulmonary lymphangitic spread of tumor.
• Subjects with prior treatments with FTIs.
• Subjects with a known or suspected hypersensitivity to any excipients in the lonafarnib formulation (Providone, Poloxamer 188, croscarmellose sodium, silicon dioxide, and magnesium stearate).