• 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