Inclusion Criteria:

1. Histologically confirmed HER2+ according to national criteria invasive carcinoma of
the breast with locally recurrent (not amenable to resection with curative intent) or
metastatic disease scheduled for a first or any subsequent metastatic treatment line.
A positive FISH test on a metastatic lesion will be acceptable (in case it is not
available for the primary tumor).

2. The patient must have at least 2 visceral or nodal "target" metastatic lesions
fulfilling all of the following imaging criteria: on diagnostic CT scan/ MRI: lesion
should be measurable according to RECIST 1.1; on FDG PET/CT: transaxial diameter of
more than 15 mm or more and Standard Uptake Value (SUV) max ≥ 2 x SUVmean of the
liver (as measured in a 3-cm-diameter spherical VOI located in the normal liver
parenchyma). If liver is suspected to be diffusely infiltrated, the lesion should
have a tracer uptake > 2.0 x SUV mean of blood pool measured in a 1-cm-diameter VOI
within the descending thoracic aorta; non confluent with adjacent lesion; target
lesion should not have been previously irradiated.

3. A biopsy of a metastatic site is required if not done previously

4. Primary tumor blocks (or 11 unstained slides) available for confirmatory central
laboratory HER2 testing.

5. Age≥18 y

6. ECOG) performance status (PS) 0 to 1

7. No significant cardiac history and current LVEF ≥ 50%

8. Adequate organ function, evidenced by the following laboratory results: Absolute
neutrophil count > 1,500 cells/mm3, Platelet count > 100,000 cells/mm3, Hb> 9 g/dL ,
Total Bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert's syndrome,
AST(SGOT) and ALT (SGPT) < 2.5 x ULN, Serum alkaline phosphatase ≤ 2.5 x ULN
(patients with bone metastases: alkaline phosphatase ≤ 5 x ULN) , Serum creatinine <
2.0 mg/dL or 177 μmol/L, International normalized ratio (INR) and activated partial
thromboplastin time or partial thromboplastin time (aPTT or PTT)<1.5x ULN (unless on
therapeutic anti-coagulation)

9. Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;

10. For women of childbearing potential a pregnancy test will be done and an agreement to
use a highly-effective form of contraception during all the study will be obtained.

11. Signed written IC approved by Ethics Committee and obtained prior to any study
procedure.

12. Completion of all necessary baseline surgical, laboratory and imaging investigations
prior to patient inclusion

Exclusion Criteria:

1. Patients with bone only metastases are not eligible, except if two of these bone
lesions satisfy the RECIST 1.1 and metabolic criteria.

2. Diffuse liver(≥ 75%)involvement on the FDG-PET/CT

3. Patients with brain metastasis as the sole site of metastatic disease and/or are
symptomatic or require therapy to control symptoms. NB: Brain metastasis are allowed
provided they are asymptomatic and/or controlled by previous radiotherapy.

4. Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic >100 mmHg)

5. Current unstable angina

6. History of symptomatic CHF of any New York Heart Association (NYHA) criteria or
ventricular arrhythmia that requires treatment

7. History of myocardial infarction within the last 6 months

8. History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab
treatment

9. Current dyspnea at rest due to complications of advanced malignancy, or other
diseases that require continuous oxygen therapy

10. Current severe, uncontrolled systemic disease

11. History of other malignancy within the last 5 years, except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
or other cancers with a similar outcome as those previously mentioned

12. Pregnant or lactating women

13. Current known uncontrolled infection with HIV, HBV, or HCV

14. Known prior severe hypersensitivity to trastuzumab

15. Patient who received lapatinib within the 15 days prior to 89Zr-trastuzumab injection

16. Patient under a prohibited concomitant therapy (Cf protocol)