-  Age ≥ 18 years

          -  Written informed consent must be given according to ICH/GCP, and national/local
             regulations

          -  Availability of peripheral blood draw for CTC blood test

          -  Tumor block or minimum 10 unstained slides of 4 μm of primary tumor must be available
             prior to registration for centralized HER2 testing

          -  ER status available

          -  Adequately excised non-metastatic and non-relapsed operable primary invasive
             HER2-negative adeno-carcinoma of the breast *:

          -  the patient should have completed either

          -  adjuvant chemotherapy or

          -  neoadjuvant chemotherapy; in this case residual invasive disease in breast or lymph
             nodes is required (no complete pathological response) no further adjuvant chemotherapy
             treatment planned. Prior chemotherapy with doxorubicin restricted to a total dose of
             360 mg/m2 or with epirubicin restricted to a total dose of 720 mg/m2 is allowed

          -  No prior use of anti-HER2 therapy for any reason or immunotherapy for BC

          -  No concomitant use of bisphosphonate therapy or denosumab for any reason. Prior use of
             these agents is allowed provided that last treatment has been received at least 4
             weeks before registration in the study

          -  No prior mediastinal irradiation except internal mammary node irradiation for the
             present BC

          -  Concomitant adjuvant hormonal therapy or radiotherapy (if applicable) is allowed upon
             physician's choice

          -  The interval between definitive surgery (neoadjuvant population) or end of adjuvant
             chemotherapy (adjuvant population) and registration must be at least 3 weeks but no
             more than 24 weeks

          -  No evidence of unresolved or unstable toxicity from prior surgery, adjuvant
             chemotherapy or radiotherapy

          -  No history of prior invasive breast carcinoma, except for the BC diagnosed and treated
             before entry. Unifocal or multifocal unilateral (one breast) or unifocal or multifocal
             synchronous bilateral breast (both breasts) cancer are acceptable if all invasive
             tumor foci are HER2- negative. History of previous ductal carcinoma in situ is allowed

          -  No history of any malignant neoplasms in the past 5 years except for curatively
             treated basal and squamous cell carcinoma of the skin

          -  No prior autologous or allogeneic stem cell transplantation

          -  No history of serious cardiac illness or medical conditions, including but not
             confined to:

          -  History of documented congestive heart failure

          -  High risk uncontrolled arrhythmias

          -  Angina pectoris requiring anti-anginal medication

          -  Clinically significant valvular heart disease

          -  Evidence of transmural infarction on ECG

          -  Poorly controlled hypertension (e.g. systolic > 180 mm Hg or diastolic > 100 mm Hg)

          -  No history of other concurrent serious diseases that may interfere with planned
             treatment, including severe pulmonary conditions

          -  Absence of 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

          -  WHO performance status 0-1

          -  No concurrent participation in another trial

          -  No clinically significant active infections