Characterization of the driver mutations in an individual metastatic breast cancer patient is critical for many reasons. Effective targeted therapies require identifying genomic alterations in the tumoral tissue. The scarce efficacy of many currently available targeted drugs may be due to the outbreak of resistant clones with different genotype that already present at the initiation of therapy. It is well known the intra-tumor heterogeneity with genetic and non-genetic factors considered as the origin of the tumor cell-clon composition. The acquisition of multiple mutations (driver and passenger), altogether with the stage of differentiation, according to the cancer stem cell hypothesis, confers to the tumor cells clinically important properties, such as resistance to therapies and seeding abilities.

Moreover, there is a current challenge in establishing whether the metastatic cells arise from the most aggressive and dominant clone in the primary tumor or the metastasic tissue diverges with substantial genetic changes very early in the evolution of the disease. Primary and metastatic tumor may have a close clonal relationship or evolve in parallel and acquire different genomic alterations. In the real life, it is plausible that both models coexist with different predominance according to the tumoral tissue and etiology.

The study hypothesizes that breast cancer metastases and primary tumors could harbor different genomic profiles related to genomic regions of interest in a clinically relevant proportion of metastatic breast cancer patients.

Moreover, the genomic aberrations found in the metastatic breast cancer tissue could also be detected in CTCs and circulating free DNA.

If true, CTCs and circulating free DNA would be convenient, non-invasive, easily accessible sources of genomic material for the analysis of mutations and other genomic aberrations.

Inclusion Criteria:

• Metastatic breast cancer confirmed by radiologic findings
• ≥ 18 years old
• Able to give signed consent
• Availability to get the paraffin block of her primary tumor.
• First metastatic relapse or tumor regrowth while on treatment for metastatic disease (progressive disease while on treatment)
• Biopsy of the metastatic site clinically indicated

Exclusion Criteria:

• Inability to get a core sample from a metastatic site
• Bone disease only (the decalcification process usually prevents an appropriate genomic study).
• Unable to drawn peripheral blood
• Unable to give the informed consent
• Coagulation disorders
• ECOG status 3-4

Women with metastatic breast cancer in which FFPE samples from the primary tumors are available and in whom a biopsy of the metastatic relapse is clinically indicated.

Investigators will offer enrollment to consecutively seen women who meet the entry criteria. Target enrollment is 40 patients