Vanderbilt-Ingram Cancer Center

Patients are being asked to take part in this research study because they have breast cancer that is positive for the estrogen receptor (ER) and negative for the human epidermal growth factor receptor 2 (HER2), and their disease has gotten worse while getting treatment with an aromatase inhibitor. The patient-s tumor must also contain a mutation in the PI3-kinase gene. This part of the study is designed to examine a lower dose of GDC-0941 (260 mg) in combination with fulvestrant to see if this dose may be more tolerable (patients will be given GDC-0941 or a matching placebo at a 2:1 ratio). Only patients whose tumor contains a mutation in the PI3 kinase gene will be allowed to enroll in this part of the study.

Criteria
 Inclusion Criteria:

 • Patients with ER-positive locally advanced breast cancer or Metastatic Breast Cancer (MBC). Postmenopausal women with locally advanced breast cancer or Metastatic Breast Cancer whose disease has progressed during or after treatment with an aromatase inhibitor. Part II: Postmenopausal women with locally advanced PIK3CA-mutant breast cancer or PIK3CA-mutant MBC that has progressed during or after treatment with an AI.

 • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

 • Patients must have measurable disease by RECIST v1.1 or bone-only disease

 • Adequate hematologic and end-organ function

 • Estrogen receptor-positive disease and HER2-negative disease

 Exclusion Criteria:

 • Prior treatment with fulvestrant, PI3K inhibitor, or mTOR inhibitor for advanced breast cancer or MBC

 • Prior treatment with > one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on > two endocrine therapies for metastatic breast cancer

 • History of malabsorption syndrome or other condition that would interfere with enteral absorption

 • History of clinically significant cardiac or pulmonary dysfunction

 • Clinically significant history of liver disease

 • Active uncontrolled autoimmune disease or active inflammatory disease

 • Immunocompromised status

 • Symptomatic hypercalcemia

 • Need for current chronic corticosteroid therapy

 • Pregnancy, lactation, or breastfeeding

 • Known untreated or active central nervous system (CNS) metastases Other protocol-defined inclusion/exclusion criteria may apply.