The goal of this clinical trial is to is to evaluate whether a correlation exists between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation, and Progression Free Survival (PFS) under PARPi and/or DNA-damaging. This proof-of-concept study is a first step to confirm the hypothesis that a dual parameter approach combining (i) longitudinal monitoring of CTC enumeration and (ii) functional assessment of HR capacity in ex vivo expanded CTCs will enable accurate prediction of therapeutic response to PARPi and cytotoxic chemotherapies, particularly those involving cross-linking DNA-damaging agents such as platinum salts in 300 adult patients witch advances/metastatic Ovarian, Breast, Prostate, or Pancreatic cancer potentially eligible to PARP inhibitor treatment as standards of care at the center Léon Bérard.

The main questions it aims to answer are:

• Correlation between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation and Progression Free Survival (PFS) under PARPi and/or DNA-damaging chemotherapy
• Proportion of patients from whom ≥1 CTC colony can be successfully isolated and expanded ex vivo under predefined culture conditions
• Distribution of CTC samples classified as HR-proficient vs HR-deficient based on assay-specific thresholds

Inclusion Criteria:

• Male or female patients ≥ 18 years at the day of signing informed consent.
• Advanced/metastatic breast, prostate, ovarian and pancreatic cancer patients potentially eligible to PARP inhibitor treatment as monotherapy or in combination as per respective SmPC (see Appendix 1) or IB if the PARPi treatment is investigational.
• Patients who have understood, dated, and signed the written voluntary informed consent form before undergoing any procedure specific to the protocol.
• Patients affiliated with or benefiting from medical insurance.

Exclusion Criteria:

• Patients with secondary malignancy with the exception of basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer, prior malignancy and no evidence of recurrence for ≥ 2 years.
• Patients presenting a psychological, familial, geographical, or social situation that, in the investigator's judgment, could potentially prevent the signing of informed consent and/or compliance with study procedures.
• Pregnant or breast-feeding women.
• Patients under judicial protection (guardianship, curatorship, or legal safeguard), adults under protection in accordance with Articles L.1121-6, L.1121-8, and L.1121-8-1 of the French Public Health Code, as well asindividuals not affiliated with a social security scheme or without equivalent health coverage.