High sensitivity to targeted agents has been observed in patients whose tumor cells present a genetic/genomic deregulation of the target (Kit mutation, ERBB2 amplification, EGFR mutations) together with addiction to the given target. More recently, activation of "alternative pathways" (Kras mutation, PI3K mutations) have been reported as a common resistance mechanism to single agent tyrosine kinase inhibitors (trastuzumab, cetuximab).

From these data has emerged the hypothesis that identification of the deregulated pathway through new molecular tools could allow to propose a more tailored targeted regimen.

Based on these concepts, numbers of phase I/II trials enrich their populations in patients presenting specific molecular alterations.

High throughput technologies (array CGH, sequencing, gene expression array) identify deregulated genes. In addition, these technologies determine whether such genomic alterations are single (expected efficacy of single agent) or multiple (rationale for combination). In a pilot study that included 135 patients, we recently performed a combination of array CGH and hot spot mutation array in order to drive patients into phase I/II clinical trials. This study led to the conclusions that high throughput technologies i. are feasible (80%) and robust, ii. identify "targetable" genomic alterations in around 40% of samples.

In the present study, the investigators will perform high throughput technologies to drive 400 metastatic breast cancer patients into specific phase I/II trials.

Inclusion Criteria:

• Men and Women with histologically diagnosed breast cancer
• Metastatic relapse or stage IV breast cancer at diagnosis
• Metastases amenable to biopsy
• Age <70 years old
• PS 0/1
• No restriction regarding the number of previous chemotherapy or endocrine therapies

Exclusion Criteria:

• Age <18
• Life expectancy <3 months
• Symptomatic or progressing brain metastases
• Progressive patients at the time of biopsy
• LVEF <50% (MUGA or ultrasonography)
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count < 1.5 x 109/L
• Platelet count < 100 x 109/L
• Haemoglobin < 90 g/L
• ASAT/ALAT > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
• Total bilirubin > 1.5 times ULN
• Creatinine >1.5 times ULN
• Corrected calcium > ULN
• Phosphate > ULN
• Abnormal blood coagulation that contra-indicates biopsy
• Patients deprived of liberty or placed under the authority of a tutor

women or men with metastatic breast cancer