A Phase I-II Study of R115777 (Tipifarnib, Zarnestra®) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Stage IIB-IIIC Breast Cancer

Inclusion Criteria:

- Bilirubin normal

- AST and ALT =< 2.5 times upper limit of normal

- LVEF normal by echocardiogram or nuclear scan

- Creatinine normal OR Creatinine clearance >= 60 mL/min

- No other invasive malignancy within the past 5 years except curatively treated basal
cell or squamous cell skin cancer or carcinoma in situ of the cervix

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to tipifarnib or other study drugs (e.g., imidazoles or
quinolones)

- No other uncontrolled illness including, but not limited to, any of the following:
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia or psychiatric illness/social situations that would
preclude study compliance

- Not pregnant or nursing

- Negative pregnancy test

- At least 1 week since prior tamoxifen or other selective estrogen receptor modulator
for prevention or for other indications (e.g., osteoporosis or prior ductal carcinoma
in situ)

- FEV1 >= 1 L* and DLCO >= 50%* [Note: *Only if baseline CT scan of chest shows
parenchymal lung disease OR there is a history of chronic obstructive or other
pulmonary disease]

- No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g.,
mastectomy, lumpectomy, or axillary dissection) for this cancer but prior sentinel
lymph node biopsy for this malignancy allowed

- No prior adjuvant chemotherapy for a previous breast malignancy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- Histologically or cytologically confirmed adenocarcinoma of the breast; clinical
stage IIB, IIIA, IIIB, or IIIC disease

- HER-2/neu-negative by DAKO Herceptest or fluorescence in situ hybridization (FISH)

- The following prior or concurrent diagnoses are allowed:

- Lobular carcinoma in situ

- Contralateral ductal carcinoma in situ

- Contralateral invasive ductal and/or lobular cancer

- Hormone receptor status:

- Estrogen and/or progesterone receptor-positive* [Note: *Patients enrolled on the
phase I portion of the trial may have estrogen and progesterone
receptor-negative disease]

- WBC >= 3,000/mm^3

- Absolute neutrophil count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- ECOG performance status 0-1

- Fertile patients must use effective contraception