DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced breast cancer for which standard curative or palliative measures do not exist or are no longer effective

  • Metastatic or unresectable disease
• HER-2 non-expressing tumor, defined as IHC 0-2+ AND FISH ratio < 2.0
• Measurable disease per RECIST guidelines OR evaluable (non-measurable) disease
• Tumor must be accessible and suitable for serial biopsy with 3 passes of a 16-gauge needle
• Failed ≥ 1 prior systemic therapy for metastatic breast cancer

• No known active brain metastases

  • Brain metastases that have been previously treated and stable for ≥ 1 month are allowed provided they were not accompanied by seizures and that a baseline brain MRI scan before study entry demonstrates no current evidence of progressive brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in the presence of liver metastases)
• Alkaline phosphatase ≤ 2.0 times ULN (≤ 5 times ULN in the presence of bone or liver metastases)
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN OR calculated or measured creatinine clearance ≥ 60 mL/min
• QTc interval of ≤ 470 ms as measured by ECG using Bazett's formula
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 forms of effective contraception (i.e., 1 barrier method and 1 other method of contraception) for ≥ 4 weeks before, during, and for ≥ 12 months after completion of study treatment
• Able and willing to provide archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic and pharmacogenomic correlative studies
• Agrees to undergo a total of 3 serial biopsies for research purposes
• Able to swallow tablets
• No malabsorption syndrome or other condition that would interfere with intestinal absorption
• No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
• No co-morbid condition(s) that, in the opinion of the investigator, would preclude safe treatment

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No active infection or fever > 38.5°C
• No HIV or hepatitis B or C positivity
• No clinically active liver disease, including active viral or other hepatitis or cirrhosis
• No history of seizures

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior therapy with either a γ-secretase or Hedgehog inhibitor

  • Patients who received prior Hedgehog antagonist GDC-0449 or gamma-secretase inhibitor RO4929097 as part of a single or limited dosing study (i.e., phase 0 study) may be eligible
• No prior allogeneic stem cell transplantation
• No prior radiotherapy to ≥ 50% of total marrow volume
• More than 3 weeks since prior radiotherapy to ≤ 5% of total marrow volume (4 weeks for radiotherapy to > 5% of total marrow volume) and recovered to < grade 2 toxicities

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

  • Patients with residual taxane neuropathy of ≤ grade 1 are eligible
• More than 30 days or 5 half-lives since prior investigational therapy or immunotherapy and recovered
• No concurrent growth factor support (e.g., Neulasta®, Neupogen®) for chronic maintenance of WBC counts or granulocyte counts
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent medications or food that may interfere with the metabolism of Hedgehog antagonist GDC-0449 and gamma-secretase inhibitor RO4929097, including ketoconazole, grapefruit juice, and/or grapefruit

• No other concurrent anticancer therapy (e.g., cytotoxic therapy, biologic therapy, radiotherapy, or hormonal therapy other than for replacement)

  • Medications that are prescribed for supportive care but may potentially have an anticancer effect (e.g., megestrol acetate or bisphosphonates) are allowed provided they were started 1 month before study enrollment
• No other concurrent investigational therapy

• Concurrent warfarin anticoagulation allowed provided all of the following criteria are met:

  • Patients are therapeutic on a stable warfarin dose
  • INR target range is ≤ 3
  • INR is monitored weekly
  • No active bleeding or pathological condition that carries a high risk of bleeding
• Other concurrent anticoagulants, including enoxaparin (Lovenox) or fondaparinux (Arixtra) allowed