Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge in ER+ mBC

Exclusion Criteria

• •HR or HER2 unknown disease.
• •HER2-positive disease based on local laboratory results \[performed by immunohistochemistry/fluorescence in situ hybridization (FISH)\].
• •Locally advanced breast cancer candidate for a local treatment with a radical intention.
• •Formal contraindication to endocrine therapy.
• •Progressing central nervous system (CNS) disease.
• •Patients with exclusive non-measurable/evaluable disease.
• •Other malignancies within the past five years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix.
• •Major surgery (defined as requiring general anaesthesia) or significant traumatic injury within four weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study.
• •Patients with an active bleeding diathesis, previous history of bleeding diathesis, or anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
• •Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
• •Are unable to swallow tablets.
• •History of malabsorption syndrome or other condition that would interfere with enteral absorption.
• •Chronic daily treatment with corticosteroids with a dose of ≥10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
• •QTc \>480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• •Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (i.e., hypocalcemia, hypokalemia, or hypomagnesemia).
• •Known hypersensitivity to any palbociclib excipients.