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 co…