Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Advanced Breast Cancer Obtention and signing of the molecular preselection consent regarding the mutational BRCA status confirmation prior to provision of the informed consent. 2. Provision of informed consent prior to any study specific procedures. 3. Male or female ≥18 years of age at the time of signing the Informed Consent Form (ICF). 4. Histologically and/or cytologically confirmed breast cancer with evidence of advanced disease (locoregionally recurrent or metastatic) not amenable to resection or radiation therapy with curative intent. 5. Patients with histologically and/or cytologically locally confirmed diagnosis of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) May 2018 criteria. 6. Patients with documented germinal mutation in Breast Cancer (BRCA)1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Patients with germinal BRCA1/2 mutations that are considered to be non-detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism," etc.) will not be eligible for the study. Patients with known germinal BRCA status prior to enrollment are considered eligible to participate. 7. of resistance to trastuzumab defined as Relapse on (neo) adjuvant treatment or within 6 months from completion, or Progression on a trastuzumab regimen for advanced disease. No limitations on the number of prior trastuzumab regimens. 8. At least one prior systemic regimen for advanced disease including a pertuzumab or T-DM1 based regimen. No limitations on the number of prior systemic regimens. 9. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1. 10. Life expectancy greater or equal to 16 weeks. 11. Patients must have evaluable or measurable disease by Computed Tomography (CT) scan or Magnetic resonance imaging (MRI), according to Response Evaluation in Solid Tumors (RECIST) 1.1 criteria. 12. Patients must have normal organ and bone marrow function within 35 days prior to administration of study treatment as defined below Hematological: White blood cell (WBC) count >3.0 x 109/L, absolute neutrophil count (ANC) ≥1.5 x 109/L, platelet count ≥100.0 x109/L, and hemoglobin ≥ 10 g/dL Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (x ULN) (≤2.0 in patients with known Gilberts syndrome) or direct bilirubin ≤ 1 x ULN; alkaline phosphatase (ALP), Aspartate aminotransferase (AST) / Serum Glutamic Oxaloacetic Transaminase (SGOT), and Alanine aminotransferase (ALT) / Serum Glutamic Pyruvate Transaminase (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN Renal: Serum creatinine ≤ 1.5 x ULN or based on a 24-hour urine test or estimated creatinine clearance ≥ 51 mL/min using the Cockcroft-Gault equation: Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72a where F=0.85 for females and F=1 for males. 13. Patients have been informed about the nature of study, including the exploratory studies and has agreed to participate and signed the ICF prior to participation in any study-related activities. 14. Males, postmenopausal and premenopausal women. Premenopausal women of childbearing potential (not undergoing to tubal ligation or hysterectomy) must have a negative blood or urine pregnancy test within 28 days prior to the start of study treatment and confirmed on Day 1 prior to commencing treatment Postmenopausal status is defined as either Prior bilateral oophorectomy; Or Age > 60 years; Or Age < 60 years and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression, and Follicle-stimulating hormone (FSH) and estradiol in postmenopausal range; Or Age < 60 years and taking tamoxifen or toremifene and FSH and plasma estradiol level in postmenopausal ranges; Or Radiation-induced castration with >1-year interval since last menses. Premenopausal status is defined as all those women who do not meet any of above criteria. Note: Documented hysterectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 highly effective forms of contraception in combination male condom plus an acceptable hormonal or non-hormonal method) throughout the study. Information must be captured appropriately within the site's source documents. Correct forms of contraception for males and females are detailed in Appendix 5: Acceptable birth control methods. 15. Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 16. Snap frozen or formalin fixed paraffin-embedded (FFPE) tumor sample is mandatory for exploratory central testing. 17. Patients must fulfil the relative field on the informed consent for donating blood samples and serial biopsies at baseline and on disease progression for the exploratory biomarker studies  Patients that have previously received any poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) for any reason, including olaparib. 2. Involvement in the planning and/or conduct of the study (applies to both Sponsor's staff and/or staff at the study site). 3. Patients simultaneously enrolled in any interventional clinical trial. 4. Patients who have received any systemic chemotherapy during the last 3 weeks prior initiating protocol therapy. 5. Patients who have had radiation therapy encompassing >20% of the bone marrow within 3 weeks prior to start of treatment, excepting for palliative radiation therapy to a small field >1-week prior to Day 1 of study. 6. Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. 7. Concomitant use of known strong Cytochrome P450 (CYP)3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, boosted protease inhibitors, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. 8. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. 9. Persistent toxicities (Common Terminology for Adverse Events (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia. 10. Patients with Myelodysplastic syndrome (MDS) / Acute myeloid leukemia (AML) or with features suggestive of MDS/AML. 11. Patients having diagnosis, detection, or treatment of another type of cancer during the last 5 years prior to initiating protocol therapy (except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, definitively treated ductal carcinoma in situ, stage 1, grade 1 endometrial carcinoma), or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≤5 years). 12. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 13. Patients considered a high medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution CT scan or any psychiatric disorder that prohibits obtaining informed consent. 14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 15. Immunocompromised patients (e.g., patients who are known to be serologically positive for human immunodeficiency virus and those with undetectable viral load). 16. Patients with a known hypersensitivity to olaparib or trastuzumab or any of the excipients of the products. 17. Clinically significant cardiovascular disease (stroke, unstable angina pectoris, or documented myocardial infarction) within 6 months prior to study entry; history of documented congestive heart failure (New York Heart Association II-III-IV); symptomatic pericarditis; documented cardiomyopathy; ventricular arrhythmias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication]. 18. Left ventricular ejection fraction below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO). 19. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment. 20. Patients currently receiving anti-coagulant therapy (low molecular weight heparin and warfarin with careful monitoring of patients are permitted), or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed). 21. Patients with pulmonary disease requiring continuous oxygen therapy. 22. Previous history of bleeding diathesis. 23. Patients with known active hepatitis (i.e. Hepatitis B or C). 24. Patients with moderate or severe hepatic impairment. 25. Chronic daily treatment with corticosteroids with a dose of ≥ 10 mg/day methylprednisolone equivalent (excluding inhaled steroids), except for prophylaxis use. 26. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation. 27. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment and in a dose < 10 mg/day methylprednisolone equivalent. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods. Patients unwilling to or unable to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations