Lapatinib Ditosylate and Akt Inhibitor MK2206 in Treating Women With Metastatic Breast Cancer

Inclusion Criteria

• •Patients must be women with histologically or cytologically confirmed Her2 positive (3+ by immunohistochemistry \[IHC\] or fluorescence in situ hybridization \[FISH\] ratio \>= 2.0) advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• •Patients must have estrogen receptor (ER) and progesterone receptor (PR) negative metastatic breast cancer or have had progressive disease following at least 1 prior hormonal therapy for ER or PR positive metastatic breast cancer
• •Patients enrolled in the expansion cohort at the MTD dose of MK-2206/lapatinib combination must agree to undergo two biopsies for research purposes (Note: we will only biopsy the MTD cohort and their tumor must be accessible for biopsy)
• •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan; patients with skin-only disease not measurable by RECIST are eligible but must have disease for which unilateral dimensions can be measured and must have monthly photographs with measurements available
• •Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%; Merck \& Co. suggest ECOG performance status of 0-1 for trials with MK-2206, but inclusion of performance status 2 patients is at the discretion of investigators
• •Leukocytes \>= 3,000/mcL
• •Absolute neutrophil count \>= 1,500/mcL
• •Platelets \>= 100,000/mcL
• •Total bilirubin within normal institutional limits
• •Magnesium within normal institutional limits
• •Potassium within normal institutional limits
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• •Creatinine =\< 1.2 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional norm
• •Lapatinib has been reported to decrease left ventricle ejection fraction (LVEF); patients with preexisting cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure will not be eligible; normal LVEF will be confirmed before starting lapatinib, and evaluations (echocardiogram \[ECHO\]/multi gated acquisition scan \[MUGA\]) continued every 3 cycles during treatment; repeat LVEF determination will be performed for any signs or symptoms suggestive of congestive heart failure
• •Patients must have developed progressive disease following at least 1 prior systemic therapy for metastatic breast cancer
• •Prior radiation therapy is allowed; however, any radiation therapy must have occurred greater than 3 weeks from the planned initiation of study treatment and any radiation-induced toxicity must have recovered to =\< grade 1 at the time of initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
• •Prior experimental (non-Food and Drug Administration \[FDA\] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies; prior therapy with TDM-1 or anti-Her2 monoclonal antibodies (i.e. trastuzumab, pertuzumab) is allowed
• •Patients must not have received allogeneic stem cell transplant
• •Patients must not have co-morbid condition(s) that, at the opinion of the investigator, prevent safe treatment
• •Patients must not be pregnant or nursing
• •Life expectancy of greater than 12 weeks
• •Women of child-bearing potential must agree to 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
• •Ability to understand and the willingness to sign a written informed consent document