Olaparib and Radiotherapy in Inoperable Breast Cancer

Inclusion Criteria: * ≥18 years of age * Histological proven breast cancer or local recurrence of breast cancer which is inoperable or/and metastatic, including inflammatory breast cancer * No participation in trial with neoadjuvant systemic treatment, except for previous contralateral breast cancer * Tumor in breast accessible for biopsy * WHO performance 0-2 * Life expectancy of at least 6 months * Adequate hematological, renal and hepatic functions * Hemoglobin 6.2 mmol/l * Leucocytes 3.0 x 10E9/l * Absolute neutrophil count 1.5x10E9/l * Platelet count 100 x 10E9/l * Total bilirubin ≤ 1.5 x ULN * ASAT/ALAT ≤ 2.5 x ULN; or in the presence of liver metastases ≤ 5 x ULN * Creatinine clearance 50 ml/min; measured or calculated * Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 21 days of study treatment. Non-childbearing potential or postmenopausal is defined as: * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments * LH and FSH levels in post menopausal range for women under 50 years of age * Radiation-induced oophorectomy with last menses \> 1 year ago * Chemotherapy-induced menopause with \> 1 year interval since last menses * Surgical sterilisation (bilateral oophorectomy or hysterectomy) * Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards * Signed written informed consent Exclusion Criteria: * Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within 3 weeks prior to start of therapy (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin ornitrosourea). Patient may continue the use of tamoxifen, aromatase inhibitor and LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids. The use of denosumab for bone disease is not allowed. * Major surgery within two weeks of starting study treatment. * Participation in other trial with investigational drug or treatment modality * Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. * Prior ipsilateral radiotherapy to the chest or breast. * Blood transfusion in the four weeks prior to study entry * Persistent toxicities (CTC ≥ grade 2) with the exception of alopecia, caused by previous cancer therapy * QT-interval \> 470 msec * Significant cardiovascular disease as defined by * History of congestive heart failure defined as NYHA class III * History of unstable angina pectoris or myocardial infarction up to 3 months prior to trial entry; * Presence of severe valvular heart disease * Presence of a ventricular arrhythmia requiring treatment; * Uncontrolled hypertension * Patients considered a poor medical risk due to: * non-malignant systemic disease * active, uncontrolled infection requiring parenteral antibiotics * a serious, uncontrolled medical disorder; examples include, but are not limited to: * uncontrolled major seizure disorder * unstable spinal cord compression * superior vena cava syndrome * extensive bilateral lung disease on HRCT scan * any psychiatric disorder that prohibits obtaining informed consent. * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. * Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy. * Patients with known active hepatic disease (i.e. Hepatitis B or C) * Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear. * Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication * Concomitant medications: * Any previous treatment with a PARP inhibitor, including Olaparib * Patients receiving the following classes of inhibitors of CYP3A4 (see Section 6.4.2 for guidelines and wash out periods) * Azole antifungals * Macrolide antibiotics * Protease inhibitors * Patients with a known hypersensitivity to olaparib or any of the excipients of the product * Breast-feeding women