Nab-paclitaxel (Abraxane) With or Without Mifepristone in Patients With Advanced Breast Cancer

This trial will find the best dose of mifepristone when given together with nab-paclitaxel (Abraxane) based on the side effects of the two drugs in patients with advanced breast cancer.

Patients will be randomized to receive nab-paclitaxel with or without mifepristone during the first treatment cycle. After the first cycle, all patients will receive nab-paclitaxel with mifepristone until their disease worsens or they experience an unacceptable side effect.

This study will test up to 4 doses of mifepristone in combination with nab-paclitaxel. The study will first test the lowest dose in a small group of patients and if they do not have bad side effects, higher doses will be tested.


Eligibility Criteria:
Inclusion Criteria:

* Patients must have metastatic (stage IV) or unresectable (cannot be removed by surgery) stage III breast cancer
* Patients must have evaluable disease
* Patients may have received adjuvant chemotherapy and up to four prior chemotherapy regimens for metastatic or locally recurrent disease and cannot have received prior nab-paclitaxel or mifepristone therapy for metastatic disease
* Patients who are estrogen receptor (ER)- and/or progesterone receptor (PR)-positive must have developed metastatic disease while on adjuvant hormonal therapy or have progression of disease after at least one hormonal therapy for advanced disease) and may have received unlimited prior hormonal therapies
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky \> 60%)
* Absolute neutrophil count \>= 1,500/mL
* Platelets \>= 100,000/mL
* Total bilirubin =\< institutional upper limit of normal (ULN)
* AST (serum glutamic oxaloacetic transaminase \[SGOT\])/ALT (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional ULN
* Creatinine =\< institutional ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Morning cortisol \>= institutional normal
* Negative serum or urine pregnancy test is required for women of child-bearing potential (able to get pregnant)
* Women of child-bearing potential and men who are sexually active must agree to use two forms of birth control prior to study entry and for the duration of study participation
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Patients may not be receiving any other investigational drugs or treatments
* Patients with known brain metastases are eligible as long as they have completed radiation to the brain and have been off of corticosteroid therapy for at least 4 weeks
* History of allergic reactions to compounds similar to mifepristone or paclitaxel/nab-paclitaxel; patients with a history of mild infusion reactions with paclitaxel who were able to continue to receive paclitaxel with corticosteroid premedications will be eligible to participate, as these cases were likely related to Cremophor and not paclitaxel
* Mifepristone may affect the way the body processes some types of drugs so they cannot be taken while on-study. These include but are not limited to non-steroidal anti-inflammatory drugs (NSAIDs) or warfarin, cyclosporine, certain benzodiazepines. The study doctor will review patient's current medications to determined if any are prohibited from the study.
* Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breastfeeding should be discontinued if patient wishes to participate in the study
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
* No history of long-term or ongoing short term use of corticosteroids is allowed