The present trial clinical proposes to randomize patients with cancer metastatic disease of the breast progressing on standard therapy to receive a treatment selected from 4 "targeted" drugs (a MEK kinase inhibitor, an mTOR kinase inhibitor, an of the enzyme involved in DNA repair PARP and an androgen receptor inhibitor) on the basis of possible presence of mutations in a panel of 61 genes analyzed on metastatic tissue from biopsy, or receive standard chemotherapy.

Inclusion Criteria:

• Patients (women or men) with histologically confirmed metastatic breast cancer
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Written informed consent obtained prior to enrollment
• Age ≥ 18 years
• Blood and tumor tissue sample available for research
• Measurable disease
• Other site accessible for biopsy, except bone lesions if this is the only accessible site, or biopsy obtained within the previous 6 months
• Medical history, blood parameters and clinical conditions do not indicate major dysfunctions of organ

To treatment:

- Maintenance of screening inclusion criteria

Exclusion Criteria:

• Presence of visceral crisis, defined according to ABC3/ESMO guidelines
• Patients with local recurrence that can be treated with surgery and/or radiotherapy alone
• Patients who have previously received palliative radiotherapy on the only site accessible to biopsy
• Patients with metastatic disease limited to bone
• Patients with metastatic disease limited to the brain, unless planned a surgical excision, in which case tissue can be collected for screening
• Severe hematopoietic, renal and/or hepatic insufficiency
• Known contraindication to biopsy
• Neoplastic pathology of different histology in the previous 5 years, except carcinoma in situ of cervical basal or squamous cell carcinoma of the skin, if adequately treated