Phase 1b/2 Trial Using Lapatinib, Everolimus and Capecitabine for Treatment of HER-2 Positive Breast Cancer With CNS Metastasis

Inclusion Criteria:

* Patients with HER2+ (immunohistochemistry \[IHC\] 3+ or fluorescence in situ hybridization \[FISH\]+ R/G \> 2.0 or silver-enhanced in situ hybridization \[SISH\]+ HER2/chromosome 17 centromere \[CEP17\] \> 2.0) breast cancer with documented central nervous system (CNS) recurrence or progression
* Must have received trastuzumab (neoadjuvant, adjuvant or metastatic setting)
* At least one measurable lesion in the brain (\>= 10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging \[MRI\]); (prior neurosurgical resection, whole brain radiation or stereotactic radiation therapy is allowed provided the patient has a measurable CNS progression \[at least one new and/or progressive measurable brain metastasis\]; measurable or non-measurable extracranial metastases allowed)
* Concurrent steroids allowed (up to equivalent of prednisone 20 mg daily, on taper or stable dose for at least 2 weeks)
* Life expectancy of \>= 12 weeks
* Previous treatment with other HER2 targeted agents allowed; (previous treatment with HER2 inhibitors and investigational drugs to be discontinued prior to starting study treatment \[at least 21 days for trastuzumab and other antibodies; at least 14 days for lapatinib; at least 5 half-lives for other agents\])
* Previous chemotherapy (adjuvant and metastatic regimens) and hormonal therapy allowed, but chemotherapy must have been discontinued at least 21 days prior to starting study treatment and hormonal therapy at least 7 days prior to starting study treatment; patients must have recovered from acute Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 grade \>= 2 side effects of previous treatments
* At least 2 weeks since prior radiotherapy or stereotactic radiosurgery, and 4 weeks since prior major surgery at time of study enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelets \>= 100 x 10\^9/L
* Hemoglobin (Hb) \>= 9 g/dL
* Serum bilirubin =\< 1.5 x upper limit of normal (ULN) (=\< 3.0 if Gilbert's syndrome)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN in patients with liver metastases)
* International normalized ratio (INR) =\< 1.5
* Adequate renal function: serum creatinine =\< 1.5 x ULN
* Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND fasting triglycerides =\< 2.5 x ULN; NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
* Signed informed consent
* Age \>= 18 years

Exclusion Criteria:

* Patients who have never received trastuzumab
* Prior treatment with an mammalian target of rapamycin (MTOR) inhibitor (including everolimus, sirolimus, temsirolimus)
* Leptomeningeal carcinomatosis as only site of CNS disease
* Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
* Patients with clinically significant interstitial lung disease or history of cardiac disease
* Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
* Prior treatment with any investigational drug within the preceding 4 weeks prior to starting study drug
* Patients receiving chronic, systemic treatment with corticosteroids (more than 20 mg/day prednisone equivalent, see inclusion criteria) or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
* Patients should not receive immunization with attenuated live vaccines within one week of starting study drug or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella and typhoid vaccine live oral (TY)21a typhoid vaccines
* Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
* Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

  * Symptomatic congestive heart failure of New York heart Association class III or IV
  * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, left ventricular ejection fraction (LVEF) \< 50% or any other clinically significant cardiac disease
  * Severely impaired lung function as defined as spirometry and diffusion capacity of the lung of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (02) saturation that is 88% or less at rest on room air
  * Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN (Note: optimal glycemic control should be achieved before starting trial therapy)
  * Active (acute or chronic) or uncontrolled severe infections
  * Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)
  * Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C ribonucleic acid polymerase chain reaction (HCV RNA PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; patients with positive results for HBV/HCV infection will be allowed in this study provided monitoring and prophylactic treatment are followed
* A known history of human immunodeficiency virus (HIV) seropositivity
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus/lapatinib (lapatinib ditosylate) (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
* Patients with an active, bleeding diathesis
* Patients on warfarin (patients on injectable blood thinners, such as Lovenox, are able to continue those)
* Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of study drug)
* Male patient whose sexual partner(s) are women of childbearing potential (WOCBP) who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
* Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
* History of noncompliance to medical regimens
* Patients unwilling to or unable to comply with the protocol