Pet Imaging as a Biomarker in Hormone Refractory postmenopausaL Women

Inclusion Criteria

• •1. Adult women (≥18 years of age) with locally advanced or metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
• •2. Histological or cytological confirmation of estrogen-receptor positive (ER+), HER2 negative breast cancer.
• •3. Postmenopausal female defined as:
• •* Age ≥55 years and one year or more of amenorrhoea
• •* Age \<55 years and one year or more of amenorrhoea, with an estradiol assay \<20pg/ml
• •* Surgical menopause with bilateral oophorectomy NOTE: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (goserelin or leuprolide) is not permitted for induction of ovarian suppression.
• •4. Breast cancer that is refractory to non-steroidal aromatase inhibitors (NSAI) (i.e. anastrozole or letrozole) defined as:
• •* Recurrence while on, or within 12 months of end of adjuvant treatment with anastrozole or letrozole; OR
• •* Progression while on, or within one month of end of anastrozole or letrozole or treatment for locally advanced or metastatic breast cancer.
• •NOTE: Letrozole or anastrozole do not have to be the last treatment prior to enrolment.
• •5. FDG-PET measurable disease defined as: at least one target lesion fulfilling following criteria:
• •* Size ≥1.5cm; AND
• •* FDG-PET avid lesion with uptake above the background liver uptake as described below: i.e. with a marked accumulation of FDG, at least 1.5-fold greater than liver SUV mean + 2 SDs (in 3cm spherical ROI in normal right lobe of liver). If liver is abnormal, target lesion should have uptake \> 2.0 x SUV mean of blood pool in 1cm diameter ROI in descending thoracic aorta)
• •NB:
• •* The target lesion can be a bone metastasis if it fulfils the above mentioned criteria.
• •* In the case the target lesion is a lymph node, the small axis should be ≥ 1.5cm.
• •6. Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrolment.
• •7. Adequate bone marrow function as shown by:
• •* Haemoglobin (HgB) ≥9.0 g/dL
• •* ANC ≥1,500/mm3 (≥1.5 x 109/L)
• •* Platelets ≥100,000/mm3 (≥100x 109/L)
• •8. Adequate liver function as shown by:
• •* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5xULN (or ≤5 if hepatic metastases are present)
• •* Total serum bilirubin ≤1.5 x ULN (≤3 ULN for patients known to have Gilbert Syndrome)
• •9. Adequate renal function as shown by Serum creatinine ≤1.5 x ULN
• •10. Fasting serum cholesterol, triglycerides and glucose
• •* Fasting serum cholesterol ≤300 mg/dL or 7.75 mmol/L
• •* Fasting triglycerides ≤2.5 x ULN
• •* Fasting glucose \< 1.5 x ULN
• •11. Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
• •12. Written and signed informed consent obtained before any trial related activity.
• •13. Availability of a FFPE core of primary breast tumor
• •14. Possibility to obtain the mandatory blood samples for the translational research studies.
• •15. For patients with accessible metastatic lesions, possibility to obtain the mandatory biopsy (FFPE and frozen) of a metastatic lesion