Prediction of Treatment Efficacy of the Combination of Palbociclib/(Letrozole or Anastrozole) in First Line Metastatic Women With Luminal, HER2 Negative Advanced Breast Cancer, Using Infrared Laser Spectroscopy Analysis on Liquid Biopsies.

Inclusion Criteria: To be enrolled in the study, patients should meet the following inclusion criteria: 1. Written informed consent before beginning specific protocol procedures including expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to the local regulatory requirements. 2. Postmenopausal women or pre/peri-menopausal women with Surgical oophorectomy (preferred) or Analogs of LHRH. 3. Performance status \< 3 (according to WHO criteria). 4. Histologically confirmed breast cancer (Luminal A or B). 5. Estrogen Receptor positive (ER \> 1%). 6. HER2 negative (score 0 or 1 by immunochemistry), FISH negative if IHC score 2. 7. Clinical stage IIIb \& IV. 8. Either: 1. Women with De novo advanced luminal HER2 negative advanced breast cancer without other prior systemic treatment for advanced disease. 2. Women with luminal HER2 negative advanced breast cancer either with secondary resistance (relapse after 2 years of adjuvant hormone therapy or within 12 months of completion of adjuvant HT) or sensitivity to adjuvant HT (relapse \> 12 months after completion of adjuvant HT). 9. Measurable or evaluable disease. 10. Hematology: * Neutrophil count ≥ 1.5 G/L, * Platelet count ≥ 100 G/L, * Leucocyte count \> 3.0 G/L, * Hb\> 9g/dl. 11. Hepatic function: * Total bilirubin ≤ 1.5 times the upper normal limit (UNL), * ASAT ≤ 2.5xUNL, * ALAT ≤ 2.5xUNL, * Alkaline phosphatase ≤ 2.5 times the upper normal limit (UNL). 12. Renal function: • Serum creatinine ≤1.5xUNL (and if Serum creatinine \>1.5xUNL, creatinine clearance ≥40 mL/min), 13. Metabolic function: • Serum calcium ≥ lower limit of normal. 14. Negative pregnancy test (urine or serum) within 7 days before registration for all women of childbearing potential. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment. 15. Patients with negative Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results. Exclusion Criteria: To be enrolled in the study, patients should meet the following exclusion criteria: 1. Male patients. 2. HER2 positive tumors or unknown HR/HER2 status. 3. Triple-negative Breast Cancer (ER\<1%). 4. Pregnant or breast-feeding women, or those who plan to become pregnant within 6 months post-treatment. 5. No willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months post-treatment. 6. Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or loco-regional disease (stages I, II \& IIIa). 7. Non-evaluable tumor. 8. Bilateral breast cancer. 9. Patients with a history of other cancer, except in situ cervical cancer or baso-cellular skin cancer, considered cured. 10. Patient has another disease, which is deemed incompatible with the inclusion in the protocol. 11. Heart, kidney, medullary, respiratory or liver failure. * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) at baseline. * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease at baseline, * Acute urinary infection, ongoing hemorrhagic cystitis at baseline. 12. Uncontrolled diabetes. 13. Symptomatic or progressive disorder of the central nervous system (CNS) at baseline. 14. Patients with positive Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results. 15. Significant psychiatric abnormalities. 16. History of hypersensitivity to studied treatment or excipients. 17. Known previous or ongoing abuse of narcotic drug, other medication or alcohol. 18. Any investigational agent within 30 days before initiation of study treatment. 19. Patient unwilling or unable to comply with study requirements.