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.

Prior treatment

• Known previous or ongoing abuse of narcotic drug, other medication or alcohol.
• Any investigational agent within 30 days before initiation of study treatment.

Other illness

• Triple-negative Breast Cancer (ER\<1%).
• Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or loco-regional disease (stages I, II \& IIIa).
• Bilateral breast cancer.
• Patients with a history of other cancer, except in situ cervical cancer or baso-cellular skin cancer, considered cured.
• Patient has another disease, which is deemed incompatible with the inclusion in the protocol.
• 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.
• Uncontrolled diabetes.
• Symptomatic or progressive disorder of the central nervous system (CNS) at baseline.
• Patients with positive Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.
• Significant psychiatric abnormalities.
• History of hypersensitivity to studied treatment or excipients.

Other

• To be enrolled in the study, patients should meet the following exclusion criteria:
• Male patients.
• HER2 positive tumors or unknown HR/HER2 status.
• Pregnant or breast-feeding women, or those who plan to become pregnant within 6 months post-treatment.
• No willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months post-treatment.
• Non-evaluable tumor.
• Patient unwilling or unable to comply with study requirements.

• To be enrolled in the study, patients should meet the following inclusion criteria:
• 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.
• Postmenopausal women or pre/peri-menopausal women with Surgical oophorectomy (preferred) or Analogs of LHRH.
• Performance status \< 3 (according to WHO criteria).
• Histologically confirmed breast cancer (Luminal A or B).
• Estrogen Receptor positive (ER \> 1%).
• HER2 negative (score 0 or 1 by immunochemistry), FISH negative if IHC score 2.
• Clinical stage IIIb \& IV.
• Either:
  • Women with De novo advanced luminal HER2 negative advanced breast cancer without other prior systemic treatment for advanced disease.
  • 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).
• Measurable or evaluable disease.
• Hematology:
  • Neutrophil count ≥ 1.5 G/L,
  • Platelet count ≥ 100 G/L,
  • Leucocyte count \> 3.0 G/L,
  • Hb\> 9g/dl.
• 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).
• Renal function:
  • Serum creatinine ≤1.5xUNL (and if Serum creatinine \>1.5xUNL, creatinine clearance ≥40 mL/min),
• Metabolic function:
  • Serum calcium ≥ lower limit of normal.
• 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.
• Patients with negative Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.