...1) Patients must provide written informed consent prior to any study procedures being performed and according to local ethics committee guidelines2) Female patients aged over 18 years3) Patients must be pre-menopausal, defined as last menstrual period within 1 year of inclusion, or with oestrogen and follicle stimulating hormone (FSH)/luteinising hormone (LH) levels compatible with ovarian function, particularly if the patient has had a hysterectomy; patient must be on effective non-hormonal contraception4) Patients must have a histological diagnosis of oestrogen receptor positive breast cancer and have relapsed or are refractory to hormone therapies, which must have included tamoxifen, goserelin and an aromatase inhibitor (AI) prior to Screening5) Patients must have performance status ≤2 ECOG scale6) Patients must be suitable for hormone therapy in the investigator's opinion7) Patients must have measurable disease according to the RECIST criteria8) Patients must have a life expectancy of >3 months9) Patients with bone metastases are eligible provided that they have evaluable sites of metastases that can be followed by x-ray, MRI/CT scan. ...

In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively)....This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics.