Patient description: The patient is a 45-year-old postmenopausal woman with cytologically confirmed breast cancer. A core biopsy revealed a 3 cm invasive ductal breast carcinoma in the left upper outer quadrant. The tumor is HER2-positive and ER/PR negative. Axillary sampling revealed 5 positive lymph nodes. CXR was remarkable for metastatic lesions. The patient is using multivitamins and iron supplements. She does not smoke or consume alcohol. She is not sexually active and has no children. She is a candidate for tumor resection and agrees to do so prior to chemotherapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-120.0,  Postmenopausal Women With ER+ HER2- Primary Breast Cancer Signed and dated informed consent form (ICF) 2. Women >=18 years 3. Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery 4. Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of ≥ 1.0 cm 5. Any clinical nodal status 6. ER+breast cancer 7. HER2 breast cancer defined as a negative in situ hybridization test or an immno-histochemistry (IHC) status of 0 or 1+ 8. Eastern Co-operative Oncology group (ECOG) performance status 0-1 9. Post-menopausal status defined as meeting at least one of the following Have undergone a bilateral oophorectomy; Age ≥60 years; Age ≥50 years and with cessation of regular menses ≥12 months and with an intact uterus in the absence of oral contraception or hormone-replacement therapy (HRT) prior to the diagnosis of breast cancer; Age <60 years and with cessation of regular menses ≥12 months and follicle stimulating hormone (FSH) and oestradiol levels in the postmenopausal range  Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays 2. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments) 3. Inflammatory breast cancer 4. Evidence of metastases 5. Patients currently receiving medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5 or strong inhibitors of CYP2C8 or that are sensitive substrates of CYP2C8 inhibition 6. Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment 7. Use of hormone-replacement therapy from <4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment 8. Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment. 9. Any of the following cardiac Mean resting QT interval corrected for heart rate (QTc) > 470 msec obtained from 3 ECGs using Fridericia's formula Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG Any factors that increase the risk of QTc prolongation or risk of arrhythmic events 10. Experience of any of the following in the preceding 6 months: coronary artery bypass graft (CABG), angioplasty, vascular stent, myocardial infarction (MI), angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade ≥2, cerebrovascular accident (CVA), transient ischaemic attack (TIA), deep venous or arterial thrombosis, pulmonary embolism, bleeding diathesis (i.e., disseminated intravascular coagulation, clotting factor deficiency) or requirement of anticoagulant therapy 11. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, 12. Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism). 13. Unexplained symptomatic endometrial disorders. 14. Refractory nausea and vomiting, uncontrolled chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9496. 15. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: absolute neutrophil count < 1.5 x 109/L, Platelet count < 100 x 109/L, Haemoglobin < 90 g/L, alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN), aspartate aminotransferase (AST) > 2.5 x ULN, Total bilirubin > 1.5 x ULN or > 3 x in case of Gilbert's Syndrome, glomerular filtration rate < 50 mL/min 16. Direct involvement in the planning and conduct of the study 17. History of hypersensitivity to AZD9496 18. History of hypersensitivity to fulvestrant and/or castor oil 19. Judgment by the investigator that the patient should not participate in the study if unlikely to comply with study procedures, restrictions and requirements In addition, the following is considered a criterion for from the exploratory genetic research: Previous allogeneic bone marrow transplant; Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection