Inclusion

          1. Signed written informed consent

          2. >= 18 years

          3. Any menopausal status:

               1. Pre-menopausal women must have commenced treatment with an LHRH agonist at

                  least 4 weeks prior to starting IMP (AZD9833 ± palbociclib, everolimus ,or
                  abemaciclib or capivasertib) and must be willing to continue to receive LHRH
                  agonist therapy for the duration of the study

               2. Post-menopausal defined according to standard criteria in the protocol

          4. Histological or cytological confirmation of adenocarcinoma of the breast

          5. Documented positive oestrogen receptor status of primary or metastatic tumour tissue,
             according to the local laboratory parameters. HER-2 negative.

          6. Metastatic disease or locoregionally recurrent disease which is refractory or
             intolerant to existing therapy(ies) known to provide clinical benefit

          7. Metastatic or locoregionally recurrent disease and radiological or objective evidence
             of progression on or after the last systemic therapy prior to starting IMP

          8. Prior chemotherapy, endocrine therapy and other therapy as follows:

               1. No more than 2 lines of chemotherapy for advanced disease

               2. Recurrence or progression on at least one line of endocrine therapy in the

                  advanced/metastatic disease setting

               3. There is no limit on the number of lines of prior endocrine therapies

               4. Prior treatment with CDK4/6 inhibitors is permitted

          9. Women of childbearing potential must agree to use a highly effective contraceptive
             measure, must not be breast feeding, and must have a negative pregnancy test prior to
             the start of dosing

         10. At least one lesion (measurable and/or non-measurable, as per RECIST 1.1 that can be
             accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or
             plain X-ray; or clinical examination. Blastic-only lesions in bone are not considered
             assessable

         11. ECOG/ WHO performance status 0 to 1, with no deterioration over the previous 2 weeks
             and a minimum life expectancy of 12 weeks

             Inclusion criteria for the paired tumour biopsy research:

         12. Disease suitable for paired baseline and on-study tumour biopsies

         13. Washout from prior fulvestrant: 6 months

         14. Washout from prior tamoxifen: 4 months

         15. Signed written informed consent for tumour biopsies

        Exclusion

          1. Intervention with any of the following

               1. Any cytotoxic chemotherapy, investigational agents/other anti-cancer drugs for
                  the treatment of advanced breast cancer from a previous treatment regimen or
                  clinical study within 14 days of the first dose of IMP

               2. Concomitant medications or herbal supplements known to be strong
                  inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates,
                  and drugs which are sensitive substrates of CYP2C9 and/or CYP2C19, and which have
                  a narrow therapeutic index. In addition: Parts E and F will exclude the
                  concomitant use of moderate CYP3A4 and/or P-gp inhibitors; Parts G and H will
                  exclude the concomitant use of moderate CYP3A4/5 inhibitors and inducers; Parts I
                  and J will exclude concomitant use of sensitive substrates of CYP3A4 and/or
                  CYP2D6 with a narrow therapeutic index."

               3. Drugs known to prolong QT and known risk of Torsades de Pointes

               4. Radiotherapy with a limited field of radiation for palliation within 1 week of
                  the first dose of IMP, except patients receiving radiotherapy to more than 30% of
                  the bone marrow/a wide field of radiation within 4 weeks of the first dose of IMP

               5. Major surgical procedure/significant traumatic injury, as judged by the
                  investigator, within 4 weeks of the first dose of IMP, or an anticipated need for
                  major surgery and/or any surgery requiring general anaesthesia during the study

          2. Any unresolved toxicities from prior therapy > CTCAE Grade 1 at the time of starting
             IMP, with the exception of alopecia.

          3. Presence of life-threatening metastatic visceral disease, as judged by the
             investigator, uncontrolled CNS metastatic disease. Patients with spinal cord
             compression and/or brain metastases may be enrolled if definitively treated (eg,
             surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start
             of IMP

          4. Past medical history of ILD (Parts E & F only)

          5. Currently symptomatic radiotherapy-induced pneumonitis (Parts E & F only)

          6. Evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses, which in the investigator's opinion makes
             it undesirable for the patient to participate in the trial or which would jeopardise
             compliance with the protocol, or active infection including hepatitis B, hepatitis C,
             and human immunodeficiency virus (HIV)

          7. Any of the following cardiac criteria

               1. Mean resting QTcF >470 msec obtained from a triplicate ECG

               2. Any clinically important abnormalities in rhythm, conduction, or morphology of
                  resting ECG (eg, complete left bundle branch block, second- and third-degree
                  heart block), or clinically significant sinus pause. Patients with controlled
                  atrial fibrillation can be enrolled

               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events such as symptomatic heart failure, hypokalaemia, congenital long QT
                  syndrome, immediate family history of long QT syndrome, or unexplained sudden
                  death at <40 years of age. Hypertrophic cardiomyopathy and clinically significant
                  stenotic valve disease

               4. LVEF <50% and/or experience of any of the following procedures or conditions in
                  the preceding 6 months: coronary artery bypass graft, angioplasty, vascular
                  stent, myocardial infarction, unstable angina pectoris, congestive heart failure
                  NYHA Grade ≥2, cerebrovascular accident, or transient ischaemic attack.

               5. Uncontrolled hypertension. Hypertensive patients may be eligible but blood
                  pressure must be adequately controlled at baseline.

               6. Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg for parts I &J

          8. Inadequate bone marrow reserve/organ function as demonstrated by any of the following
             lab values

               1. ANC <1.5 × 109/L

               2. Platelet count <100 × 109/L

               3. Haemoglobin <90 g/L

               4. ALT >2.5 × ULN

               5. AST >2.5 × ULN

               6. TBL >1.5 × ULN or >3 × ULN in the presence of documented Gilbert's Syndrome

               7. GFR <50 mL/min

          9. Clinically significant abnormalities of glucose metabolism, as defined by any of the
             following at screening (Parts I and J only):

               1. Patients with diabetes mellitus type I or diabetes mellitus type II requiring
                  insulin treatment.

               2. HbA1c ≥8.0% (63.9 mmol/mol).