The purpose of this study is to assess the efficacy, safety and tolerability of 2 dosing regimens of BIIB021 in combination with exemestane in women whose HR+ breast cancer had progressed following treatment with a nonsteroidal aromatase inhibitor (AI).

Inclusion Criteria:

• Age 18 years of age

• Must have histologically or cytologically confirmed estrogen receptor- positive or progesterone receptor-positive, incurable, locally advanced, or metastatic breast cancer.

• Must have disease progression during treatment with a nonsteroidal AI for locally advanced or metastatic disease, or relapse during treatment or within 12 months of discontinuation of treatment in the adjuvant setting.

• Must be a postmenopausal female.

• Must have measurable or evaluable disease.

  • Measurable disease is defined as >=1 lesion with a diameter of >=10 mm
  • Evaluable disease is defined as bone lesions evaluable by plain X ray, CT scan, or MRI. Lesions identified only by radionuclide bone scan are not allowed.

• One prior chemotherapy regimen for advanced mBC is allowed.

• Prior radiotherapy is allowed.

• Must be able to swallow and retain oral medication.

• ECOG performance status of <=2

• Required laboratory values

  • Plasma cortisol and adrenocorticotropic hormone (ACTH) levels that are not suggestive of adrenal insufficiency unless on replacement therapy for known adrenal insufficiency.

Exclusion Criteria:

• HER2 overexpressing tumor.
• History of central nervous system (CNS) metastasis.
• Previous treatment with exemestane or treatment with an Hsp90 inhibitor.
• Use of proton pump inhibitors.
• Known history of or positive test result for hepatitis B or C or HIV.
• History of gastrectomy or major surgery to small intestine.