Inclusion Criteria:

• The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.
• The subject's breast cancer is negative for HER2.
• The subject has recurrent or metastatic breast cancer that is refractory to a nonsteroidal aromatase inhibitor and has either disease progression or disease recurrence.
• Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole.
• For subjects enrolled in Phase 2, either archival tumor samples must be available, or the subject must be willing to undergo a fresh biopsy.
• In Phase 2, at least 30 subjects in each arm must have measurable disease
• The subject is a postmenopausal female.
• If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least 2 months before starting study treatment.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• The subject has adequate organ and marrow function.
• The subject has no other diagnosis of malignancy or evidence of other malignancy for 2 years before screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix).
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.

Exclusion Criteria:

• The subject has received prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR.
• Certain restrictions on prior therapies apply.
• The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline.
• The subject has untreated, symptomatic, or progressive brain metastases.
• The subject has only non-measurable lesions, other than bone, skin, or chest wall metastasis
• The subject has to start cytotoxic chemotherapy due to rapid progressive disease involving major organs.
• The subject has prothrombin time/ International Normalized Ratio (PT/ INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal.
• The subject has uncontrolled significant intercurrent illness.
• The subject has a baseline corrected QT interval (QTc) > 470 ms.
• The subject has a diagnosis of uncontrolled diabetes mellitus.
• The subject is known to be positive for the human immunodeficiency virus (HIV).
• The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation(s).
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.