Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1

Inclusion Criteria:

* Patients with histologically proven HER-2 positive
* Newly diagnosed or recurrent (after surgery) stage IV disease (TNM/AJCC v.7).
* Patients must have measurable (RECIST v. 1.1) or evaluable disease
* Performance status (PS) 0-3 (WHO)
* Age ≥ 70 years of age, or ≥ 60 years old with required number of dependencies
* Life expectancy of more than 12 weeks
* Previous adjuvant chemotherapy/anti HER-2 therapy after surgery is allowed, given that the time interval from end of previous treatment to initiation of treatment for metastatic disease is ≥ 6 months.
* Up to one line of anti-HER therapy (trastuzumab or lapatinib) is allowed in combination with hormone therapy for hormone sensitive metastatic breast cancer.
* Adequate organ function
* Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

* No brain metastases that are untreated, symptomatic, or require steroids to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first study treatment.
* No prior chemotherapy for metastatic disease is allowed
* No prior treatment with pertuzumab is allowed
* No history of exposure to the following cumulative doses of anthracyclines:
* Doxorubicin or liposomal doxorubicin \> 360 mg/m2
* Epirubicin \> 720 mg/m2
* Mitoxantrone \> 120 mg/m2
* Idarubicin \> 90 mg/m2
* If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
* No history of palliative radiotherapy within 14 days of randomization
* No history of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin
* No current uncontrolled hypertension (persistent systolic \> 180 mmHg and/or diastolic \> 100 mmHg)
* No LVEF below 50%
* No history of significant cardiac disease defined as:
* Symptomatic CHF (NYHA classes II-IV)
* High-risk uncontrolled arrhythmias
* History of myocardial infarction within 6 months prior to randomization
* Clinically significant valvular heart disease
* No angina pectoris requiring anti-angina treatment
* No peripheral neuropathy of Grade ≥ 3 per NCI CTCAE version 4.0.
* No current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus)
* No major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
* No history of receiving any investigational treatment within 28 days of randomization
* No history of intolerance (including Grade 3-4 infusion reaction) to trastuzumab
* No unwillingness or inability to comply with the requirements of the protocol as assessed by the investigator
* 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 in the trial