PD0332991/Paclitaxel in Advanced Breast Cancer

Inclusion Criteria: * Patient must have histologically or cytologically-confirmed metastatic breast cancer. Any ER, PR or Her2 status is allowed. * Tumor must express Retinoblastoma (Rb) protein, as defined as any measureable staining by immunohistochemistry * Male or female and \> 18 years of age on the day of signing informed consent. * Patient must have received \< prior cytotoxic regimens for metastatic breast cancer. This does not include cytoxic regimens used in the adjuvant setting. * Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy \> 3 months. * patient on the dose-escalation portion of the trial must have evaluable disease, defined as either measurable (by RECIST) or non-measurable disease (e.g. bone mets, pleural effusion or lymphangitic spread). Measurable disease is required for patients in the expanded RP2D cohort. * The subject must have adequate organ function, defined as follows: Bilirubin \< 1.5 x upper normal limit or calculated creatinine clearance \> 60 mL/min, and for subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x upper normal limit * For subjects without extensive bone metastases: alkaline phosphatase levels \< 2.5 x upper normal limit . * For subjects with extensive bone metastases: alkaline phosphatase levels \< 5 x upper normal limit . * The subject must have adequate marrow function, defined as follows * Absolute neutrophil count (ANC) \>1500/mm * Platelets \> 100,000/mm * Hemoglobin \> 9 g/dL * Female patient of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to the use of effective methods of contraception while on study. * Patient must be capable of, and must voluntarily agree to participate by giving written informed consent. * Patient must be able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis. * Prior taxane therapy in the adjuvant or metastatic setting is allowed. * Concomitant use of biphosphonates is allowed. * Patients with stable, treated CNS disease are eligible. Exclusion Criteria: * Patient who has had chemotherapy, radiotherapy or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be \< Grade 1. * patients less than 4 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia. * Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. Oral corticosteroids for control of CNS symptoms are allowed. * Patient has known hypersensitivity to the components of study drug or its analogs. * The subject has uncontrolled intercurrent illness including, but not limited to Ongoing or active infection * Diabetes mellitus * Hypertension * Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months. * Patient has baseline neuropathy of \> grade 2 * Patients who have known allergic reactions to Paclitaxel or IV Contrast Dye despite standard prophylaxis. * The subject is pregnant or breastfeeding * The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required. * The subject is unable eor unwilling to abide by the study protocol or cooperate fully with the investigator or designee.