Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor

Estrogen hormone receptor-positive metastatic breast cancer who failed to non steroidal aromatases inhibitors in patients who are eligible for everolimus+exemestane treatment

Inclusion criteria

• Eligible for everolimus+exemestane treatment as required by the marketing authorisation conditions

• Women (or men) with histologically-proven Estrogen Receptor-positive (ER+) and/or Progesterone Receptor-positive (PR+) / Human Epidermal growth factor Receptor 2-negative (HER2-) metastatic breast adenocarcinoma or locally advanced disease who cannot be treated with surgery and/or radiation therapy
• Postmenopausal women
• Asymptomatic if visceral disease
• Second line hormonotherapy or more for metastatic or locally advanced disease after recurrence or progression following a non-steroidal aromatase inhibitor (in adjuvant or metastatic setting)

• Eligible for the biopsy
• Progressive disease under endocrine therapy at the time of inclusion
• Treatment with everolimus and exemestane not yet started
• Patients with metastases that can be biopsied, except bone metastases
• Measurable or evaluable disease
• Age ≥18 years
• WHO Performance Status 0/1
• Provision of signed and dated, written informed consent prior to any protocol specific procedure, including biopsy
• Patient with social insurance coverage

Exclusion criteria

• Contraindications for everolimus+exemestane treatment
• Previous treatment with an anti-mTOR therapy
• More than 1 previous line of chemotherapy in metastatic setting
• Life expectancy <3 months
• Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug)
• Haematopoietic function or organ impairment as shown by the following criteria:

• Polynuclear neutrophils <1.5 x 10⁹/L
• Platelets <100 x 10⁹/L
• Haemoglobin <90 g/L
• Alanine aminotransferase (ALAT) / aspartate aminotransferase (ASAT) >2.5 x ULN in the absence of or >5 x upper limit of normal (ULN) in the presence of liver metastases
• Bilirubin >1.5 x ULN
• Creatinine clearance ≤50 mL/min (measured or calculated by Cockcroft and Gault formula)
• Calcium and phosphate >ULN
• Abnormal coagulation or any other medical situation contraindicating biopsy
• Bone metastases when this is the only site of biopsiable disease
• Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
• Individuals deprived of liberty or placed under the authority of a tutor