A Phase II Trial of Tipifarnib (R115777, Zarnestra™) in Combination With Fulvestrant (Faslodex®) in Postmenopausal Hormone Receptor-Positive Breast Cancer

Inclusion Criteria: * Patients must have histologically or cytologically confirmed adenocarcinoma of the breast * Patients must be postmenopausal * Patients must have stage IV disease or inoperable locally advanced disease * Patients must have ER- and/or PR-positive disease as determined by their local pathology laboratory * 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) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan; all sites of disease should be noted and followed * Prior hormonal therapy as adjuvant therapy and/or for metastatic disease is permitted; patients previously treated with two or more prior doses of fulvestrant are not eligible; patients who have received one prior dose of fulvestrant within 28 days are eligible so long as they meet other eligibility criteria * Patients must have ECOG performance status 0-2 (Karnofsky \>= 60%) * Patients must have life expectancy of greater than 3 months * Leukocytes \>= 3,000/uL * Absolute neutrophil count \>= 1,500/uL * Platelets \>= 100,000/uL * Total bilirubin =\< 2 mg/dL * AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal * Creatinine less than or equal to 1.5 times the institutional upper limits of normal * Patients must be disease-free of prior invasive malignancies for \>= 5 years with the exception of: curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix * Patients must have the ability to understand and the willingness to sign a written informed consent document * Patients who have had previous therapy with farnesyltransferase inhibitor Exclusion Criteria: * Patients who have had 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 who have had prior chemotherapy for metastatic disease are not eligible; prior adjuvant or neoadjuvant chemotherapy is allowed * Patients may not be receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777, Zarnestra™) or other agents used in the study (e.g., imidazoles, quinolones) * Presence of rapidly progressive, life-threatening metastases; this includes patients with extensive hepatic involvement (\> 50% of the liver involved), symptomatic lymphangitic metastases, or brain or leptomeningeal involvement * Concomitant anticancer treatment with the following exceptions: (1) bisphosphonates for bone metastases, (2) a GnRH analog is permitted if the patient had progressive disease on a GnRH analog plus a SERM or an AI; the GnRH analog may continue but the SERM or AI must be discontinued * Grade 2 or more peripheral neuropathy * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with tipifarnib or other agents administered during the study.; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated