Randomized, Double Blind, Multicentric Phase III Trial Evaluating the Safety and Benefit of Adding Everolimus to Adjuvant Hormone Therapy in Women With Poor Prognosis, ER+ and HER2- Primary Breast Cancer Who Remain Free of Disease After Receiving 3 Years of Adjuvant Hormone Therapy
1. Women ≥ 18 years of age,
2. Histologically proven invasive unilateral or bilateral breast cancer (regardless of
3. Any T, M0
4. At least 4 positive lymph nodes if initial surgery, or at least 1 positive lymph node
after neo-adjuvant chemotherapy or hormone therapy
5. 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
6. Initial tumor completely resected (surgery could have been done before or after
neoadjuvant chemotherapy/hormone therapy)
7. Having received at least 2 years and 10 months but not more than 3 years and 6 months
of adjuvant hormone therapy. Hormone therapy could be either tamoxifen, letrozole,
anastrozole or exemestane.
8. No clinically or radiologically detectable metastases at time of inclusion.
9. WHO Performance status (ECOG) of 0 or 1.
10. Adequate hematological function (neutrophil count >= 2x109/l, platelet count >= 100x
11. Adequate hepatic function: ASAT and ALAT ≤ 2.5 ULN, alkaline phosphatases ≤ 2.5 ULN,
total bilirubin ≤ 2 ULN.
12. Adequate renal function: serum creatinine ≤ 1.5 ULN.
13. Signed written informed consent.
1. Any local, regional or metastatic evolution.
2. Any clinically or radiologically suspect and non-explored damage to the contra
3. Previous cancer (excepted cutaneous baso-cellular epithelioma or uterine peripheral
epithelioma) in the preceding 5 years, including invasive controlateral breast
4. Patients already included in another ongoing therapeutic trial involving an
experimental drug for which follow-up is required.
5. Pregnant or breast-feeding patients. Adequate birth control measures should be taken
during study treatment phase.
6. Patients with severely impaired lung function (e.g. Chronic Obstructive Pulmonary
Disease, respiratory insufficiency, Interstitial Lung Disease)
7. Positive serology for HIV infection or hepatitis C.
8. Chronic carrier of HBV (positive Antigen HbS in the blood)
9. Patients with chronic infection
10. Uncontrolled diabetes defined as glycated haemoglobinemia > 7%
11. Uncontrolled hypercholesterolemia (cholesterol >400 mg/dl under adequate therapy).
12. Hypersensitivity to the active substance, to other rapamycin derivatives or to any of
13. Patients with other concurrent severe and/or uncontrolled medical disease or
infection which could compromise participation in the study.
14. Patients with any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the