AKT Inhibitor in Oestrogen Positive Breast Cancer

Inclusion Criteria: 1. Written informed consent 2. WHO performance status 0-1. 3. Able to swallow \& retain oral medication. 4. Patients who fall in to either category (a) or (b): 1. Post-menopausal patients 2. Pre-menopausal patients who also meet at least one of the criteria (i), (ii) or (iii) below: i) hysterectomy or bilateral fallopian tube ligation at least 6 weeks ago plus a negative pregnancy test. ii) true abstinence iii) willing to have pregnancy testing and use 2 forms of contraception 5. Female patients, aged 18 years and over, with histological confirmation of ER positive invasive breast carcinoma. 6. Stage 1/2/3 or Stage 4 with primary tumour in the breast amenable to biopsies. New primary breast tumours (ipsi- or contra-lateral) despite prior endocrine treatment for an earlier primary breast tumour with at least 12 months interval between cessation of endocrine therapy and Visit 1 are eligible. 7. Scheduled to have chemotherapy based on tumour characteristics and local treatment protocols. 8. Tumours large enough to provide sufficient tissue to be taken by core-cut or tru-cut biopsy to provide tissue sections for the marker assays. Exclusion Criteria: 1. Prior treatment for breast cancer except new primary breast tumours arising despote prior endocrine treatment for an earlier primary breas tumour with at least 12 months interval between cessation of endocrine therapy and Visit 1 (see inclusion criteria 6). 2. Known ER negative tumour. 3. Female patients with histological confirmation of ER+ve invasive breast carcinoma not scheduled to have chemotherapy 4. Exposure to potent inhibitors or inducers of CYP3A4 or CYP2D6 or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St Johns Wort). 5. Clinically significant abnormalities of glucose metabolism 6. Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment. 7. Spinal cord compression or brain metastases. 8. Evidence of severe or uncontrolled systemic disease. 9. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc)\>450 msec obtained from 3 consecutive ECGs; - 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. * Any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2. * Uncontrolled hypotension. 10. Absolute neutrophil count \<1.5 x 10,000,000,000/L 11. Platelet count \<100 x 10,000,000,000/L. 12. Haemoglobin \<90 g/L 13. ALT \>2.5 times ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases. 14. Elevated ALP is not exclusionary if due to the presence of bone metastasis and liver function is otherwise considered adequate 15. Total bilirubin \>1.5 times ULN if no liver metastases or \>3 times ULN in the presence of liver metastases. 16. Creatinine \>1.5 times ULN concurrent with creatinine clearance \<50 ml/min; confirmation of creatinine clearance is only required when creatinine is \>1.5 times ULN 17. Proteinuria \>3+ on dipstick analysis. 18. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5363. 19. History of hypersensitivity to active or inactive excipients of AZD5363 or drugs with a similar chemical structure or class to AZD5363. 20. Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs. 21. Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. 22. Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent 23. Previous allogeneic bone marrow transplant. 24. Known immunodeficiency syndrome. 25. Pregnant or lactating patients