Inclusion criteria:

          1. Female ≥ 18 years

          2. Post-menopausal

          3. Minimum life expectancy 12 weeks

          4. Histological confirmation of ER+ve breast cancer on primary tumour at diagnosis/on
             biopsy of metastasis

          5. Histological confirmation of HER2 negative breast cancer on primary tumour at
             diagnosis/on biopsy of a metastasis

          6. Clinical or histological confirmation of metastatic or locally advanced disease not
             amenable to curative surgical resection

          7. ECOG 0-2 with no deterioration over previous 2 weeks

          8. Measurable or non-measurable disease

          9. Adequate bone marrow and organ function

         10. Progressive disease whilst receiving third generation aromatase inhibitor for locally
             advanced or metastatic BC or relapsed with metastatic disease whilst receiving third
             generation AI in adjuvant setting

         11. Radiological or objective clinical evidence of recurrence or progression on or after
             last systemic therapy prior to enrolment

         12. ≤3 prior lines of endocrine therapy for ABC

         13. ≤ 1 line of cytotoxic chemotherapy for ABC

         14. Suitable for further endocrine therapy

         15. Availability of archival tumour sample or fresh biopsy

         16. Informed consent

         17. Normal cardiac function

        Exclusion criteria:

          1. Previous treatment with fulvestrant or inhibitors of RET pathway

          2. Last dose chemotherapy, immunotherapy targeted therapy, biological therapy or tumour
             embolisation <21 days (<6 weeks for nitrosurea or mitomycin C) prior to study
             treatment

          3. Last dose of palliative radiotherapy <7 days prior to study treatment

          4. Rapidly progressive visceral disease not suitable for further endocrine therapy

          5. Spinal cord compression or brain/meningeal metastases unless asymptomatic, treated and
             stable and not requiring steroids for ≥ 4 weeks study treatment

          6. Any of the following cardiac criteria: Significant cardiac event, superior vena cava
             syndrome, NYHA classification of heart disease ≥2 within 12 weeks before
             randomisation, or presence of cardiac disease that increases risk of ventricular
             arrhythmia; History of arrhythmia which is symptomatic or requires treatment,
             symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic
             sustained ventricular tachycardia; Congenital long QT syndrome; History of QT
             prolongation associated with other medications that required discontinuation of that
             medication; QTcB >480msec on screening ECG

          7. Electrolyte values: Potassium <4.0 mmol/L despite supplementation, or above CTCAE
             Grade 1 upper limit, at randomisation; Magnesium below the normal range despite
             supplementation, or above CTCAE Grade 1 upper limit, at randomisation; Calcium
             (ionised or serum) below the normal range despite supplementation, or above Grade 1
             upper limit, at randomisation

          8. Creatinine clearance <30 ml/min. Patients with creatinine clearance <50 mL/min will
             start at a permanently reduced vandetanib dose of 200 mg.

          9. Major surgery (excluding placement of vascular access) within 4 weeks before study
             treatment

         10. Evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension, active bleeding diatheses, or active infection including hepatitis B,
             hepatitis C and HIV

         11. With the exception of alopecia, any unresolved toxicities from previous therapy
             greater than CTCAE grade 1 before study treatment

         12. Elevated ALP in absence of bone metastasis

         13. History of hypersensitivity to active or inactive excipients of vandetanib or
             fulvestrant

         14. Evidence of dementia, altered mental status or any psychiatric condition that would
             prohibit understanding or rendering of informed consent

         15. Participation in another study with investigational product during last 30 days

         16. Inability or unwillingness to comply with study procedures, including inability to
             take regular oral medication