SONIA

Patients must meet the following inclusion criteria to be eligible for enrollment:

1. Adult women (≥ 18 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of loco-regional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
2. Documentation of histologically or cytologically confirmed diagnosis of estrogen-receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based on local laboratory results. In case ER ≤ 10% and PR >10% the ER and PR expression need to be confirmed in a referral center. Tumor must be HER2-negative as defined by ASCO-CAP guidelines [6]. If HER2 status is unavailable then testing must be performed/repeated prior to randomization.
3. Previously untreated with any systemic anti-cancer therapy for loco-regional recurrent or metastatic HR+ disease.
4. Women who are not post-menopausal must use LHRH agonist. Postmenopausal status is defined as:
   1. Prior bilateral surgical oophorectomy, or
   2. Spontaneous cessation of regular menses for at least 12 consecutive months without OAC
   3. In case of doubt serum estradiol <20 umol/l and follicle stimulating hormone (FSH) levels >15 IU/L at screening
5. Measurable disease as defined per RECIST v.1.1 (see Appendix 3) or bone-only disease. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
7. Adequate organ and marrow function defined as follows:
   1. ANC ≥1,000/mm3 (1.0 x 10e9 /L);
   2. Platelets ≥50,000/mm3 (50 x 10e9 /L);
   3. Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution;
   4. Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease);
   5. AST and/or ALT ≤3 x ULN (≤5.0 x ULN if liver metastases present);
8. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1, except alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion.
9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
10. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study before any study-specific activity is performed.