Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer:

Inclusion Criteria: * Age ≥ 18 years old * Female * ECOG performance status ≤ 1 * Weight ≥ 35 kg * Histological diagnosis of invasive breast adenocarcinoma that is estrogen receptor-positive (ER-positive) and HER2- negative, as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines and performed according to local testing. In addition, only tumours with Proliferation Index Ki67 ≥ 15% or histology grade III are accepted. * Agreement to perform new study related biopsies to provide tissue samples * MammaPrint genomic high risk score according to centralised testing, except for specific conditions as mentioned below. Mammaprint will only be tested for luminal B breast tumours with either Proliferation Index Ki67 ≥ 15% or histology grade III tumours. (Testing to be done during screening period). MammaPrint result status at time of termination of all other screening procedures * MammaPrint is high risk: subject may be randomized. * MammaPrint is low risk: subjet can not be randomized. * MammaPrint result is not yet known: If the MammaPrint result is not known at time of termination of all other screening procedures, the investigator is allowed to randomize the subject and start study treatment without waiting for the result of the MammaPrint in the following situations: (Ki67 \> 20 % or grade III) and Age\<50 years+ cN0 OR Age ≥ 50 years + cN+ • Tumour size: * If subject is cN0: tumour size ≥ 2 cm, as determined by MRI imaging. * If subject is cN1, cN2 or cN3: tumour size ≥ 1.5 cm, as determined by MRI imaging. The requirement for an MRI is not applicable in the case of medical contraindications to perform MRI (e.g., obesity or claustrophobia). In this situation, tumour evaluations should be performed by ultrasound. * Multifocal, multicentric unilateral or bilateral breast adenocarcinoma tumours are allowed provided that all biopsiable foci are ER+/HER2- according to local testing and all foci are able to receive SBRT treatment within the defined dosimetric constraints. In some cases a separate biopsy of every focus is not mandatory, but only if every of the following conditions are present: -small focal lesion -lesion in close proximity to the main primary cancer from which a biopsy was taken * the investigator and the radiologist consider the lesion to be clearly related to the main primary breast cancer from which a biopsy was taken * the lesion will be removed during the same lumpectomy than the main primary breast cancer For bilateral, multifocal or multicentric disease, the site selected for pre-treatment biopsy should correspond to the site of largest measurable disease meeting eligibility criteria. The location of tumour biopsy site (laterality, quadrant, position from the nipple and type of imaging modality to guide biopsy) should be collected. * Serum pregnancy test (for subjects of childbearing potential) negative within 2 weeks prior to first dose of study administration. * Women of childbearing potential must agree to use 1 highly effective method of contraception during the screening period, during the course of the study and at least 12 months after the last administration of study treatment. it is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. * Adequate bone marrow function as defined below: * Absolute neutrophil count ≥1500/µL, i.e. 1.5x10\^9/L * Hemoglobin ≥ 9.0 g/dL * Platelets ≥100000/µL, i.e. 100x10\^9/L * Adequate liver function as defined below: \- Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome ≤ 3 x UNL is allowed \- AST (SGOT) ≤ 3.0 x ULN * ALT (SGPT) ≤ 3.0 x ULN * Adequate renal function as defined below: * Creatinine ≤ 1.5 x UNL or eGFR ≥ 40ml/min/1.73m² * Adequate coagulant function as defined below: * International Normalized Ratio (INR) ≤ 1.5 x ULN * Completion of all necessary screening procedures within 28 days prior to randomisation (except if written differently). * Willingness to provide tissue and blood samples for immuno-monitoring and translational research activities * Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF performed in routine is accepted if done within 6 months prior to beginning of screening. * Signed Informed Consent form (ICF) obtained prior to any study related procedure. Inclusion criterion for phase II only (all phase II subjects): • Tumour sample provided for central PD-L1 IHC assessment. (Testing done during screening period). Inclusion criterion applicable to FRANCE only (all safety run-in and phase II subject): • Affiliated to the French Social Security System (applicable only to subjects treated in France) Exclusion Criteria: * Pregnant and/or lactating women. * Subject with a significant medical, neuro-psychiatric, substance abuse or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study. * TNM stage cT4 breast cancer including inflammatory breast cancer * Presence of any distant metastasis * Contra-indication for treatment by paclitaxel, doxorubicin or cyclophosphamide, or known allergy to any tested substances or any excipients (e.g; chemotherapy or immunotherapy formulations). Contra-indication for subjects with known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine (this is a contra-indication for treatment with oleclumab). * Previously known contra-indication for treatment by radiation therapy such as rare genetic disorders associated with DNA repair disorders such as ataxia-telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Fanconi anemia. * Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis) within the past 3 years. NOTE: Subjects with childhood atopy or asthma, vitiligo, alopecia, Grave's disease, Hashimoto's thyroiditis, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded * Prior malignancy active within the previous 5 years, except for localised cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence. Examples include basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast * Known history of, or any evidence of active, non-infectious pneumonitis. * Active infection including: * Tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice) * Hepatitis B (known positive HBV surface antigen (HBsAg) result). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. * Hepatitis C. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, transient ischemic attack, or stroke within the previous 3 months, unstable arrhythmias, and/or unstable angina * Medical condition requiring current systemic anticoagulation, or a history of congenital hypercoagulable condition. Subjects taking aspirin at doses \< 325 mg per day are eligible provided that prothrombin time is within the institutional range of normal. Use of local anticoagulation for port maintenance is permitted. * Subjects with history of venous thrombosis in the past 12 months prior to the scheduled first dose of study treatment (oleclumab). * Diabetes mellitus Type 1 or poorly controlled Type 2 diabetes mellitus defined as a screening hemoglobin A1C ≥ 8 % or a fasting plasma glucose ≥ 160 mg/dL (or 8.8 mmol/L) * Any live (attenuated) vaccine within 30 days of planned start of study therapy. * Prior systemic immunosuppressive medication (excluding corticosteroids) within 30 days of planned start of study therapy. * Prior radiation therapy to the ipsilateral breast. * Prior immunotherapy, including tumour vaccine, cytokine, anti-CTLA4, PD-1/PD-L1, including durvalumab, blockage or similar agents. * Concomitant use of other investigational drugs * Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Subjets with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or oleclumab may be included only after consultation with the Study Physician. * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent. * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Prior organ transplantation * Subjects with urinary outflow obstruction Exclusion criterion applicable to FRANCE only • Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.