A Phase II Study of Ovarian Function Suppression And ExemesTane with or without PalbocIclib in PreMenopausal Women with ER positive / HER-2 negative MetAstatic Breast Cancer (FATIMA)

INTERVENTION: MEDICINAL PRODUCT{S}: Palbociclib Not applicable CONDITION: 9499 Metastatic Breast Cancer – Oncology ; Not applicable Not applicable PRIMARY OUTCOME: Name: Progression Free Survival (PFS)* as assessed by the Investigator. ;Timepoints: Primary Endpoint: ‐ Progression Free Survival (PFS)* as assessed by the Investigator. *PFS will be defined as the time from randomization to the time of disease progression or death for both treatment arms. ;Measure: Primary Endpoint: ‐ Progression Free Survival (PFS)* as assessed by the Investigator. *PFS will be defined as the time from randomization to the time of disease progression or death for both treatment arms. SECONDARY OUTCOME: Name: Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for ? 24 weeks ;Timepoints: Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for ? 24 weeks ;Measure: Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for ? 24 weeks Name: Objective Response (OR): Complete Response (CR) or Partial Response (PR). ;Timepoints: Objective Response (OR): Complete Response (CR) or Partial Response (PR). ;Measure: Objective Response (OR): Complete Response (CR) or Partial Response (PR). Name: Overall Survival (OS) ;Timepoints: Overall Survival (OS) ;Measure: Overall Survival (OS) Name: Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0) ;Timepoints: Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0) ;Measure: Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0) INCLUSION CRITERIA: Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study: 1. Adult women (= 18 years of age) with metastatic or locally advanced breast cancer (histologically or cytologically proven diagnosis of adenocarcinoma of the breast) not amenable to curative treatment by surgery or radiotherapy. 2. ER positive tumour: Histological or cytological confirmation of estrogen and/or progesterone‐receptor positive, as determined by routine IHC. Positivity is defined as =1% positive stained cells. The receptor status determined by utilizing an assay consistent with local laboratory standards. 3. HER2 negative breast cancer as confirmed by IHC, SISH or FISH. 4. Premenopausal women : (definition of a real menopause is not a simple task in these relatively young women, owing to the potential effect of prior chemotherapy and /or endocrinal therapy particularly OFS) defined either by: i. Any age below 40 years , irrespective