Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer

Inclusion Criteria:

   - Germline BRCA 1/2 Mutation Positive

   - Women and men at least 18 years of age or older.

   - Histologically confirmed invasive adenocarcinoma of the breast

   - HER2 negative breast cancer as defined by ASCO-CAP criteria

   - Tumor greater than or equal toT1, N0-3

   - No evidence of distant metastasis

   - Adequate bone marrow, hepatic, and renal function

   - ECOG performance status 0 or 1

Exclusion Criteria:

   - Any other previous antitumor therapies for the current cancer event. Treatment for
   ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and
   radiation.

   - Evidence of distant metastasis apparent prior to randomization

   - Patients with inflammatory breast carcinoma

   - Malignancy within the last 3 years, except: Stage 1 melanoma which does not require
   any further treatment after adequate surgical excision; adequately treated non
   melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade
   1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which
   has been disease free for a year; Other solid tumors including lymphomas (without bone
   marrow involvement) curatively treated with no evidence of disease for 5 years.

   - Previous or concomitant systemic anti cancer therapies used for the treatment of
   cancer in the last 3 years.

   - Prior treatment with a PARP inhibitor in any disease setting

   - Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors

   - Patients who are unwilling or unable to use a highly effective method of contraception
   as outlined in this protocol

   - Major surgery within 14 days prior to study entry

   - Known history of cardiac disease, for example : Myocardial infarction or symptomatic
   cardiac ischemia within 24 weeks before screening; Congestive heart failure New York
   Heart Association Class III or IV; History of clinically significant ventricular
   arrhythmias within one year prior to randomization; History of Mobitz II second degree
   or third degree heart block, uncontrolled hypertension.

   - Active clinically significant infection

   - Clinically significant bleeding diathesis or coagulopathy

   - Non healing wound, ulcer or bone fracture

   - Known hypersensitivity to any of the components of talazoparib

   - Patients with myelodysplastic syndrome/acute myeloid leukemia

   - Patients with uncontrolled seizures.

   - Any evidence of other disease or any concomitant medical or psychiatric problems which
   in the opinion of the Investigator would prevent completion of treatment