Everolimus trIal for Advanced prememopausaL Breast Cancer Patients

Inclusion Criteria:

* Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative surgery.
* Histological confirmation of estrogen and/or progesterone-receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2 -) breast cancer.

ER/PR positive: nuclear reaction \> 1%, HER2 negative: HER2; IHC 0,1+ or FISH/CISH (-) in case of IHC 2+

* Patients who:

  * received Tamoxifen for at least 6 months during adjuvant treatment and recurred during or within 24 months after the end of adjuvant treatment completion,
  * progressed during tamoxifen treatment for advanced disease.
* Pre-menopausal status was defined as either :
* The patient has a history of regular menstrual periods within 12 weeks prior to study enrollment
* The patient has FSH and E2 levels with in pre-menopausal range based on local laboratory assessments measured (i.e, FSH ≤ 40 mIU/mL and E2 ≥10 pg/mL)within 12 weeks prior to study enrollment.
* ECOG performance status of 0,1, or 2
* At least one measurable lesion or mainly lytic bone lesions in the absence of measurable disease(RECIST1.1)
* Adequate bone marrow, hepatic, and renal function
* Adequate bone marrow and coagulation function as shown by:
* Absolute neutrophil count (ANC) ≥ 1.5 109/L;Platelets\>100 x109/L;Hemoglobin (Hgb) \> 9.0g/dLINR \< 2
* Adequate liver function as shown by:
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5x ULN (or \<5 if hepatic metastases are present)
* Total serum bilirubin \< 1.5 x ULN (\<3 x ULN for patients known to have Gilberts Syndrome)
* Adequate renal function as shown by:
* Serum creatinine\< 1.5 x ULN
* Fasting serum cholesterol \<300 mg/dL or 7.75 mmol/L and fasting triglycerides \<2.5 x ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved.
* Written informed consent

Exclusion Criteria:

* Patients who have received endocrine treatment other than Tamoxifen for adjuvant or metastatic/locally advanced breast cancer.
* Patients who have received goserelin at adjuvant setting
* Patients who received more than one line of chemotherapy for metastatic or locally advanced breast cancer
* Previous treatment with mTOR inhibitors.
* Another malignancy within 5 years prior to enrollment with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.
* Symptomatic brain or other CNS metastases
* Patients receiving chronic treatment with immunosuppressive agents.
* Any severe and/or uncontrolled medical conditions, eg. currently active infection
* Pregnant or lactating
* Patients unwilling to or unable to comply with the protocol.