A Biomarker Study of Palbociclib + Fulvestrant for Second, and Third Line of Postmenopausal Women With hr+/her2- Advanced Breast Cancer

Exclusion Criteria

• •8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• •9. Patients must be treated by palbociclib+fulvestrant according to their Summary of Product Characteristics (SmPC) described bellow as a reminder :
• •Adequate organ and marrow function defined as follows:
• •* ANC \>1,500/mm3 (1.5 x 109/L);
• •* Platelets \>100,000/mm3 (100 x 109/L);
• •* Hemoglobin \> 9 g/dL (90 g/L);
• •* Serum creatinine \<1.5 x Upper Limit of Normal (ULN) or estimated creatinine clearance \>60 ml/min as calculated using the method standard for the institution;
• •* Total serum bilirubin \<1.5 x ULN (\<3 ULN if Gilbert's disease);
• •* AST and/or ALT \<3 x ULN (\<5.0 x ULN if liver metastases present);
• •* Alkaline phosphatase \<2.5 x ULN (\<5 x ULN if bone or liver metastases present).
• •10. Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade \<1 (except alopecia).
• •11. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
• •12. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• •13. Patients covered by health insurance
• •1. Prior treatment with any Cyclin-Dependent Kinase (CDK) inhibitor or fulvestrant will not be allowed. Previous treatment with Everolimus will be allowed.
• •2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, peritoneal\], pulmonary lymphangitis, and over 50% liver involvement).
• •* QTc interval \>480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
• •* any of the following within 6 months of inclusion: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade \<2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
• •* impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade \>1.
• •* prior hematopoietic stem cell or bone marrow transplantation.
• •* known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant.
• •* known or possible hypersensitivity to fulvestrant or to any palbociclib excipients.
• •* known human immunodeficiency virus infection.
• •6. Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or palbociclib+fulvestrant administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• •7. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
• •8. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before inclusion in the current study.