Prospective and Multicentric Study Evaluating DNA Double-strand Breaks (DSBs) REpair Factors (POLQ, Shieldin Complex and 53BP1) Expression as Biomarker of PARP Inhibitor Resistance in Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.
The purpose of this study is to assess whether expression of not only POLQ/Polθ, but also Shieldin complex and/or 53BP1 are correlated with primary and/or acquired resistance to PARPi (Poly(ADP-Ribose) Polymerases inhibitors) in a sub-population of locally advanced or metastatic breast cancer patients and vary regarding type and location of gBRCA1/2 mutations. This translational research program is composed of two multicentric, non-randomized prospective studies in patients with HER2-negative locally advanced or metastatic breast cancer: * The main study concerns 80 patients eligible for PARPi (according to the investigators).PARPi treatments (talazoparib or olaparib) will be administered and dosed according to the standard of care administration. * The sub-study concerns 40 patients in progression disease under PARPi alone. For each included patient in the main study or sub-study, tumor biopsy specimen and blood samples will be collected at different times during the study.
• Women (or men) aged ≥ 18 years with histologically proven breast cancer
• Metastatic relapse or locally advanced breast cancer
• No-HER2 overexpression or amplification
• Triple-negative (defines as ER\<1%, PR\<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and/or PR ≥ 1%) breast cancer
• Patients with metastases that can be biopsied except bone metastases. At baseline, if patients already have an archived biopsy from a secondary or a primary site (if stage IV) of their current disease, this material can be used for the study, provided that, it was collected within 3 months prior enrollment and a frozen and a FFPE sample are both available for research
• ECOG Performance Status ≤ 2
• Patients must have measurable or evaluable disease according to RECIST v1.1
• Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
• Any number of prior lines therapy are allowed
⁃ Current treatment with PARP inhibitor not yet started
⁃ Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
⁃ Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
⁃ Patient affiliated to a Social Health Insurance in France
• Women (or men) aged ≥ 18 years with histologically proven breast cancer
• Metastatic relapse or locally advanced breast cancer
• No-HER2 overexpression or amplification
• Triple-negative (defines as ER\<1%, PR\<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and or PR ≥ 1%) breast cancer
• Patients with metastases that can be biopsied except bone metastases
• ECOG Performance Status ≤ 2
• Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
• Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
• Patient affiliated to a Social Health Insurance in France