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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
120
For each included patient, tumor biopsy specimen and blood samples will be collected at baseline visit (before the first dose of PARPi treatment). During the treatment period: blood samples will be scheduled every 8 weeks (i.e. 2 cycles). At the time of progression: tumor biopsy and blood samples will be collected.
For each included patient, tumor biopsy specimen and blood samples will be collected as soon as possible after progression (before initiation of the post PARPi anti-tumoral treatment).
Institut Bergonie
Bordeaux, France
RECRUITINGCentre Francois Baclesse
Caen, France
RECRUITINGCentre Jean Perrin
Clermont-Ferrand, France
RECRUITINGCentre Georges Francois Leclerc
Dijon, France
WITHDRAWNCentre Hospitalier Départemental Vendée
La Roche-sur-Yon, France
RECRUITINGCentre Oscar Lambret
Lille, France
RECRUITINGCHU de LIMOGES
Limoges, France
RECRUITINGCentre Leon Berard
Lyon, France
RECRUITINGInstitut Paoli Calmettes
Marseille, France
RECRUITINGCentre de Cancerologie Du Grand Montpellier
Montpellier, France
RECRUITING...and 15 more locations
Main study: the primary endpoint is the Area under the Receiver Operating Characteristic Curve (ROC Curve) of POLQ expression to identify patients presenting progressive disease or death at 6 months under PARPi alone (primary resistance).
Progression will be determined using RECIST v1.1 criteria.
Time frame: 6 months for each patient
Sub-study: the primary end point is the rate of patients presenting loss of Shieldin complex and/or 53BP1.
Time frame: 1 month for each patient
Main study: Progression-Free Survival defined as the time from inclusion until progression according to RECIST v1.1 criteria or death from any cause, whichever occurs first.
Time frame: 12 months for each patient
Main study: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.
Time frame: 12 months for each patient
Main study: Duration Of Response defined as the time from initial objective response until progression according to RECIST v1.1 criteria or death from any cause.
Time frame: 12 months for each patient
Sub-study: expression of the Shieldin complex and 53BP1.
Time frame: 1 month for each patient
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