FUnctional Selection of Advanced Breast Cancer Patients for Talazoparib Treatment Using the REpair Capacity (RECAP) Test

Inclusion Criteria: * WHO performance status 0-2 * Locally advanced breast cancer without options for treatment with curative intent or metastatic breast cancer * Objective progressive disease (PD) according to RECIST within 4 months prior to study entry * The breast cancer must be either * high grade (Bloom \& Richardson grade 3) ER positive (\>10%) and HER2 negative primary breast cancer, or * triple negative (ER\<10%, PR\<10% and HER2 negative), or * any Bloom \& Richardson grading and receptor status and also * at least one metastatic lesion must have a proven HRD phenotype based on a RECAP test not treated with anticancer therapy thereafter or * the patient must have a proven germline or somatic BRCA1 and/or BRCA2 mutation The Bloom \& Richardson grading is always based on the primary tumor. The receptor status can be based on the primary tumor or a metastatic lesion whichever comes latest. * The site of the metastatic lesion (or primary tumor in case it is still in situ) should be easily amendable for biopsy. NB lung metastases (high risk of hemato/pneumo-thorax) and bone metastases (not suitable for RECAP test because calcifications interfere with experimental procedures) are excluded. The local guidelines will be used for stopping and r estarting of anticoagulation. Bilirubin \<1.5 ULN (except elevated bilirubin due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin) and both AST and ALT \<5x ULN in case a liver biopsy is planned. * The tumor must be HRD, defined as HRD identified by the RECAP test determined just before the start of potential Talazoparib treatment within this study (also in case a proven germline BRCA1/2 mutation is present). * Maximum of four prior lines of chemotherapy for advanced disease; Patients who received platinum compounds are eligible if they have had at least a progression free interval of four months. * Measurable or evaluable disease according to RECIST 1.1 criteria (appendix 2) * Life expectancy ≥ 3 months * Hemoglobin ≥ 10 g/dL (6,2 mmol/L) and ANC of ≥ 1.5 x 109 /L * Platelets \>100 x 10e9/L * Hepatic function as defined by total serum bilirubin ≤ 1. 5 x ULN (except elevated bilirubin due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin), ASAT and ALAT \< 3 x ULN or \<5 x ULN in case of liver metastasis * Adequate renal function as defined by either serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula) * Negative pregnancy test (urine/serum) for female patients with childbearing potential * Written informed consent Exclusion Criteria: * Any psychological condition potentially hampering compliance with the study protocol * Any treatment with investigational antitumor drugs within 28 days prior to receiving the first dose of investigational treatment; or within 21 days for standard chemotherapy; or within 14 days for weekly scheduled chemotherapeutic regimens or endocrine therapy * Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1 or 2 x 8 Gy for pain palliation, then seven days interval after the last radiation should be maintained * Known persistent (\>4 weeks) ≥ Grade 2 toxicity from prior cancer therapy (except for alopecia grade 2) * Symptomatic brain or leptomeningeal metastases. Patients completely free of symptoms and without corticosteroids for at least four weeks after adequate treatment by resection and/or irradiation could be eligible (consult PI). * Women who have a positive pregnancy test (urine/serum) and/or who are breastfeeding * Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence) * Concomitant use of P-gp inhibitors or inducers or BCRP inhibitors (see Appendix A) * Any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) * Uncontrolled infectious disease (such as Human Immunodeficiency Virus HIV-1 or HIV-2 infection) or known active hepatitis B or C * Recent myocardial infarction (\< six months) or unstable angina