MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess for a decrease in phosphorylated (phospho)-protein kinase B (Akt) (Ser\^473) levels in tissue after a pre-surgical trial of weekly MK2206 (Akt inhibitor MK2206) (2 doses) in patients with operable invasive breast cancer.

SECONDARY OBJECTIVES:

I. To evaluate the effects of MK2206 on the immunohistochemical expression of other phosphatidylinositide 3-kinase (PI3K)/AKT pathway biomarkers on pre-and post-MK2206 tumor tissue, such as phospho-S6 kinase.

II. To assess modulation of PI3K/AKT signaling following MK2206 use with reverse-phase protein microarray analysis.

III. To explore whether phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations demonstrate different modulation of PI3K/Akt-pathway signaling as compared to tumors with loss of phosphatase and tensin homolog (PTEN).

IV. To explore whether MK2206 alters PI3K/Akt pathway signaling differently in hormone receptor-positive/human epidermal growth factor receptor (HER)2-negative tumors, as compared to triple-negative or HER2-positive breast cancers.

V. To evaluate whether tumor proliferation, as measured by Ki-67 staining of breast tumor cells, is reduced in patients taking MK2206 pre-surgically and correlate Ki-67 modulation with changes in PI3K/AKT signaling.

VI. To determine safety and tolerability of MK2206 in patients with early-stage breast cancer.

VII. To collect fasting blood for evaluation of predictive markers of drug effect, such as markers in the insulin growth-factor receptor pathway (i.e., fasting insulin, c-peptide, insulin-like growth factor \[IGF\]-1, and IGF binding protein \[BP\]-1 and 3), as well as modulation of phospho-markers in peripheral blood mononuclear cells.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) on days -9 and -2, and undergo segmental resection or total mastectomy on day 0.

After completion of study treatment, patients are followed up for 4 weeks.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have histologically-confirmed operable invasive breast cancer and have undergone core needle biopsy with an anticipated surgical resection for residual disease after enrollment
* Patients must have clinical stage I-III invasive breast (invasive tumor must be clinically at least \>= 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; this includes cores underneath ultrasound-guidance
* Patients are planning to undergo surgical treatment with either segmental resection or total mastectomy (required: 2 doses of weekly MK-2206 prior to surgery; the first dose will be at day -9 \[+/- 1 day\] and second dose at day -2 \[+/- 1 day\] in relation to surgery \[day 0\])
* Patients may have a history of contralateral breast cancer, provided there is no evidence of recurrence of the initial primary breast cancer
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky \>= 80%)
* Leukocytes \>= 3,000/ul within 28 days of registration
* Platelets \>= 100,000 /uL within 28 days of registration
* Hemoglobin (Hgb) \>= 9 g/dL within 28 days of registration
* Creatinine =\< 1.5 x upper limit of normal (ULN) within 28 days of registration
* Prothrombin time (PT), partial thromboplastin time (PTT) =\< 1.2 x ULN within 28 days of registration
* Total bilirubin =\< 1.5 x ULN within 28 days of registration
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN within 28 days of registration
* Patients of childbearing potential must have a negative serum or urine pregnancy test beta-human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication
* Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
* Patient must be able to swallow oral tablets
* Ability to understand and the willingness to sign a written informed consent document
* Patients must agree to biomarker assessment of pre-treatment diagnostic core biopsy tissue and the surgical resection tissue (i.e. excision or mastectomy); also, must agree to pre- and post-treatment fasting blood biomarker collection

Exclusion Criteria:

* Patients may not have any known evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases) or locally recurrent breast cancer
* Patients with inflammatory breast cancer are not eligible
* Patients with prior chemotherapy or radiation therapy within 6 months of study entry are not eligible (i.e. patient who have received neoadjuvant therapy are not eligible)
* Patients may not be receiving any other investigational agents, including other inhibitors of PI3K, Akt, or mammalian target of rapamycin (mTOR)
* Men diagnosed with breast cancer
* Patients may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 used in the study
* Patients with known diabetes which is poorly controlled diabetes (hemoglobin A1c \[HBA1C\] \>= 8%) should be excluded; if patient is taking metformin, must have been taking this medication for \> 3 months, as metformin is thought to impact PI3K/Akt signaling
* Baseline corrected QT interval (QTc) \> 470 msec will exclude patients from entry on study; patients with a baseline bundle branch block will be excluded
* 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
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK2206
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible