Safety Study of Adding Everolimus to Adjuvant Hormone Therapy in Women With High Risk of Relapse, ER+ and HER2- Primary Breast Cancer, Free of Disease After Receiving at Least One Year of Adjuvant Hormone Therapy

Prior treatment

• Patient already included in another ongoing therapeutic trial involving an unlicensed drug for which follow-up is required
• Patient with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study (e.g. patient who regularly require systemic steroids to control co-morbid disease)

Other illness

• Any local, or regional recurrence or metastatic disease
• Any clinical or radiological suspicion of malignant or pre-malignant disease in the contralateral breast
• Previous cancer (excepted basal cell carcinoma of the skin or in situ carcinoma of the cervix) in the preceding 5 years, including invasive contralateral breast cancer
• Patient with significantly impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)
• Positive serology for HIV infection or hepatitis C
• Chronic carrier of HBV (positive Antigen HbsAg positive in the blood)
• Patient with chronic infection
• Known hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients
• Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Lab values

• Uncontrolled diabetes defined as glycated haemoglobin , HbA1c \>7%
• Uncontrolled hypercholesterolemia (cholesterol \>300 mg/dl under adequate therapy)

Other

• Patients with pN1mi as sole nodal involvement
• Patient who is pregnant or breast-feeding. Adequate birth control measures should be taken during the study treatment phase

• Female ≥18 years of age,
• Histologically proven invasive unilateral or bilateral breast cancer (regardless of the morphological subtype),
• Any T, M0
• Patient with high risk of relapse according to one of the conditions below:
  • at least 4 positive lymph nodes if the patient had primary surgery
  • or at least 1 positive lymph node if surgery was conducted after neo adjuvant chemotherapy or hormone therapy of at least 3 months duration
  • or 1-3 positive lymph nodes (pN1a, b, c) at primary surgery AND EPClin score ≥3.32867 Note: Access to primary tumor for patients with 1-3 node positive is mandatory. Patient with EPClin score \<3.32867 will not be randomized, but will be followed yearly during 10 years
• ER+ and HER2 negative : Hormone receptor positive is defined as any staining on the primary tumor, HER2 negativity is defined as IHC 0-1+, or \[IHC 2+ and FISH or CISH non-amplified\]
• Primary tumor completely resected (deep margins and overlying skin involvement allowed if fully resected)
• Patients who will begin an adjuvant hormone therapy or have received a maximum of 4 years of adjuvant hormone therapy. Hormone therapy could be either +/- LH-RH agonists, letrozole, anastrozole or exemestane.
• No clinically or radiologically detectable metastases at time of inclusion.
• WHO Performance status (ECOG) of 0 or 1.
• Adequate hematological function (neutrophil count ≥2x10⁹/L; platelet count ≥ 100x10⁹/L)
• Adequate hepatic function: AST and ALT ≤2.5 ULN, alkaline phosphatases ≤2.5 ULN, total bilirubin ≤2 ULN
• Adequate renal function: serum creatinine ≤1.5 ULN
• Signed written informed consent