Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer

Inclusion Criteria:

- Patients must have histologically confirmed operable, invasive adenocarcinoma of the
breast and have undergone core-needle biopsy with an anticipated surgical resection
for residual disease after enrollment

- Clinical stage IB-IIIC invasive breast (invasive tumor must be >= T1c by radiograph
or palpation)

- Patients must have available tissue from core biopsies for biomarker assessment

- It is recommended that at least 4 cores be performed with 12-gauge (or smaller
gauge) needles, including cores underneath ultrasound-guidance

- Patients planning to undergo surgical treatment with either segmental resection or
total mastectomy required

- Patients may have a history of contralateral breast cancer, provided there is no
evidence of recurrence of the initial primary breast cancer

- Patients must agree to biomarker assessment of pre-treatment diagnostic core-biopsy
tissue and the surgical resection tissue (i.e., excision or mastectomy) and also
agree to pre- and post-treatment fasting blood biomarker collection

- Patients may not have any known evidence of distant metastatic disease (i.e., lung,
liver, bone, or brain metastases) or locally recurrent breast cancer

- No inflammatory breast cancer

- Estrogen receptor, progesterone receptor, and human epidermal growth factor (HER)2
positive or negative

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (Karnofsky PS
80-100%)

- Menopausal status not specified

- White blood cell count (WBC) >= 3,000/μL

- Platelet count >= 100,000/μL

- Hemoglobin >= 9 g/dL

- Creatinine =< 1.5 times upper limit of normal (ULN)

- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.2 times ULN

- Total bilirubin =< 1.5 times ULN

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times ULN

- Negative pregnancy test

- Women of childbearing potential must use two forms of contraception (hormonal,
barrier method of birth control, or abstinence) prior to study entry and for the
duration of study participation

- Not pregnant or nursing

- Patient must be able to swallow oral tablets

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to Akt inhibitor MK2206 used in the study

- No known diabetes that is poorly controlled (glycosylated hemoglobin [HBA1C] >= 8%)

- No baseline QTc > 470 msec

- No baseline bundle branch block

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- No concurrent combination antiretroviral therapy for human immunodeficiency virus
(HIV)-positive patients

- More than 6 months since prior chemotherapy or radiotherapy

- Concurrent metformin allowed provided patient has been taking it for > 3 months

- No prior neoadjuvant therapy

- No other concurrent investigational agents, including other inhibitors of PI3K, Akt,
or mammalian target of rapamycin (mTOR)