Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors After a CDK4/6 Inhibitor

1.1 Inclusion criteria Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply: Informed consent 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses. Age 3. Subject must be 19 years of age or older at the time of signing the informed consent form. Type of patient and disease characteristics 4. Patients with HR+/HER2- metastatic or inoperable breast cancer 5. Disease progression following treatment with endocrine therapy(ies) and CDK4/6 inhibitor 6. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below * Hemoglobin ≥ 10.0 g/dL. Red blood cell/plasma transfusion is not permitted within 2 week prior to screening assessment. * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Granulocyte colony-stimulating factor administration is not permitted within 1 week prior to screening assessment. * Platelet count ≥ 100 x 109/L. Platelet transfusion is not permitted within 1 week prior to screening assessment. * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) if no liver metastases; or ≤ 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline. * Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN * Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test : Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females and F=1 for males. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 8. Patients must have a life expectancy ≥ 16 weeks. 9. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessment. Reproduction 10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential. Postmenopausal is defined as: * Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50 * 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) OR Pre/peri-menopausal, ie, not meeting the criteria for being post-menopausal. * Pre-/peri-menopausal women can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin). Participants must have concomitant treatment with LHRH agonists (goserelin or leuprorelin) - which must have been started 3 weeks before Cycle 1 Day 1 - and must be willing to continue on it for the duration of the study. 11. Negative pregnancy test (urine and/or serum) for women of childbearing potential within 28 days of study treatment and confirmed prior to treatment on day 1. 12. Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential Specific criteria for each cohort 13. \<For cohort A\> Patients with known germline or somatic mutations of BRCA1 or BRCA2 14. \<For cohort B\> Patients with known somatic mutations of BRCA1, BRCA2, or other DDR genes (including ATM(ataxia telangiectasia mutated), ATR, BRIP1, PALB2, CHEK1, CHEK2, FANC family, RAD51 family, etc.) Patients with alteration in other DDR genes can be discussed with the principal investigator at the molecular tumour board. 1.2 Exclusion criteria Medical conditions 1. As judged by the investigator, any evidence of condition or illness which in the investigator's opinion makes it undesirable for the patient to participate in the trial. 2. Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. 3. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. 4. Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) v5.0 grade 2) caused by previous cancer therapy, excluding alopecia grade 2. 5. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS(myelodysplastic syndrome)/AML(Acute Myelogenous Leukemia ) 6. 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 (up to 10 mg prednisone/day or equivalent) before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. 7. Patients considered a poo