BKM120 and Fulvestrant for Treating Postmenopausal Patients With Estrogen Receptor-Positive Stage IV Breast Cancer

Inclusion Criteria:

* Patient must be ≥ 18 years of age
* Patient must be a postmenopausal woman, defined by one of the following criteria:

  * Women ≥ 60 years
  * Women aged 45-59 years with spontaneous cessation of menses ≥ 12 months prior to registration
  * Women aged 45-59 years with cessation of menses of duration \< 12 months or secondary to hysterectomy AND an follicle-stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
  * Women aged 45-59 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
  * Status post bilateral surgical oophorectomy
* Patient must have a negative serum pregnancy test within 48 hours before starting study treatment (if a woman of childbearing potential)
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patient must have histologically or cytologically confirmed invasive breast cancer that is stage IV or metastatic (histologic/cytologic confirmation of recurrence preferred, but not required)
* Patient must have a representative tumor tissue specimen available; archival tissue is allowed
* Either the primary or the metastatic tumor must be positive for estrogen receptor (\>= 1% tumor cell staining by immunohistochemistry or an Allred Score of \>= 3 by immunohistochemistry)
* Patient must have at least one site of measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
* Patient must have had no more than 3 lines of systemic therapy (including endocrine therapy) for metastatic disease to be eligible for phase IB and the last 10 patients of Cohort C; there is no limitation on the numbers of prior systemic therapies for phase IA and the first 2 patients of Cohort C
* Patients who are currently taking fulvestrant without disease progression are eligible
* Patient must have a life expectancy of \>= 12 weeks
* Patient must have adequate oran function as defined as:

  * Absolute neutrophil count (ANC) \>= 1500/uL
  * Platelet count \>= 100,000/uL
  * Hemoglobin \>= 9 g/dL
  * Serum creatinine =\< 1.5 x upper limit of normal (ULN)
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =\< 3.0 x ULN if liver metastases are present)
  * Serum bilirubin =\< ULN (or =\< 1.5 x ULN if liver metastases are present; or total bilirubin =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
  * Serum amylase =\< ULN
  * Serum lipase =\< ULN
  * Magnesium \>= the lower limit of normal
  * Potassium within normal limits for the institution
* Patient must have international normalized ratio (INR) =\< 2
* Patient must have fasting plasma glucose =\< 120 mg/dL (6.7 mmol/L)
* Patient must have total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed)
* Patient must be able and willing to sign the consent form

Exclusion Criteria:

* Patient must not have received prior treatment with a P13K inhibitor
* Patient must not have a known hypersensitivity to BKM120 or to its excipients
* Patient must not have untreated brain metastases; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial if the patient is:

  * 4 weeks from therapy completion (including radiation and/or surgery)
  * Clinically stable at the time of study entry
  * Not receiving corticosteroid therapy
* Patient must not have acute or chronic liver disease, renal disease, or pancreatitis
* Patient must not have any of the following mood disorders as judged by the Investigator or a Psychiatrist

  * Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
  * Greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
* Patient must not meet the cut-off score of \>= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of \>= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or select a positive response of 1, 2, or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
* Patient must not have \>= grade 2 diarrhea
* Patient must not have active cardiac disease including any of the following:

  * Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
  * QTc \> 480 msec on screening electrocardiogram (ECG) (using the QTcF formula)
  * Angina pectoris that requires the use of anti-anginal medication
  * Ventricular arrhythmias except for benign premature ventricular contractions
  * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
  * Conduction abnormality requiring a pacemaker
  * Valvular disease with document compromise in cardiac function
  * Symptomatic pericarditis
* Patient must not have a history of cardiac dysfunction including any of the following:

  * Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
  * History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  * Documented cardiomyopathy
* Patient must not have poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (defined by fasting glucose \>120 mg/dL or hemoglobin \[Hb\] A1c \> 7%)
* Patient must not have any other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
* Patient must not have significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes; diffusion capacity of carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
* Patient must not have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated
* Patient must not have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\]) =\< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
* Patient must not have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to: St. Johns wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits
* Patient must not be currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes unless the treatment can either be discontinued or switched to a different medication prior to starting study drug; please refer to Table 5-2 for a list of prohibited QT prolonging drugs with risk of Torsades de Pointes
* Patient must not be receiving chronic treatment with steroids or another immunosuppressive agent; Note: topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed; patients with previously treated brain metastases who are on stable low dose corticosteroids treatment (e.g. dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible
* Patient must not be currently treated with drugs known to be moderate or strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A (CYP3A) unless the treatment can be discontinued or switched to a different medication prior to starting study drug (please note that co-treatment with weak inhibitors of CYP3A is allowed)
* Patient must not have received chemotherapy or targeted anticancer therapy =\< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug
* Patient with any residual toxicities may not be enrolled unless all toxicities recover to =\< grade 1 before starting the trial
* Patient must not have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =\< 5 effective half lives prior to starting study drug; patient must have recovered from side effects of such therapy
* Patient must not have received wide field radiotherapy =\< 4 weeks or limited field radiation for palliation =\< 2 weeks prior to starting study drug; patient must have recovered from side effects of such therapy
* Patient must not have undergone major surgery =\< 2 weeks prior to starting study drug; patient must have recovered from side effects of such therapy
* Patient must not be currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant
* Patient must not have a known diagnosis of human immunodeficiency virus (HIV) infection
* Patient must not have a history of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix