Inclusion Criteria:

1. Written informed consent prior to admission to this study.

2. Aged ≥ 25 years of age.

3. Histologically confirmed ER+ve primary or metastatic breast cancer.

4. Locally advanced or metastatic breast cancer treated with 1st line AI treatment
with either a documented objective response (CR/PR) or disease stabilisation (SD)
for at least 6 months prior to disease progression.

5. Postmenopausal as defined by any of the following criteria:

1. Prior bilateral oophorectomy OR

2. Women ≥ 60 years OR,

3. Women aged 45 - 59 years with amenorrhoea for ≥ 12 months and an intact uterus
OR,

4. Women aged ≤ 55 years who have undergone hysterectomy and their FSH levels are
within the postmenopausal range (as per local practice) OR,

5. Women aged ≤ 55 years who have been on Hormone Replacement Therapy (HRT) within
the last 12 months and are therefore not amenorrhoeic but their FSH levels are
within the postmenopausal range (as per local practice) OR,

6. Radiation menopause (at least 3 months previously) with FSH levels within the
postmenopausal range OR,

7. Chemotherapy or gonadotropin-releasing hormone (GnRH) induced amenorrhoea for >2
years and luteinisizng hormone (LH) FSH levels in the postmenopausal range.

6. ECOG performance status 0 to 2.

7. Measurable and/or evaluable sites of locally advanced or metastatic disease that can
be accurately assessed by CT/MRI scan at baseline and follow up visits (RECIST v1.1).

8. Adequate organ function as defined by (Haemoglobin (Hb) ≥ 9 g/dL; Absolute Neutrophil
Count (ANC) ≥ 1.5 x 109/L; Platelet count (Plts) ≥ 100 ≥ 109/L; White Blood Cell
(WBC) ≥ 3.0 x 109/L; Serum albumin ≤ 1.5 upper limit of normal (ULN); Aspartate
Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 x ULN if no
demonstrable liver metastases or ≤ 5 x ULN in the presence of liver metastases;
alkaline phosphatase (ALP) ≤ 5 x ULN; Total bilirubin ≤ 1.5 x ULN if no demonstrable
liver metastases or ≤ 3 x ULN in the presence of liver metastases; Creatinine ≤ 1.5 x
ULN or creatinine clearance >50ml/min).

9. Life expectancy of ≥3 months.

Patients with bone metastasis are eligible provided they have evaluable metastases sites
that can be followed (X-Ray or MRI/CT scanning). Patients on established bisphosphonate
treatment for at least 3 months are eligible for entry into the trial and are allowed to
continue with bisphosphonate treatment.

Exclusion Criteria:

1. Human epidermal growth factor Receptor-2 (HER2) positive cancer.

2. Discontinuation of current AI prior to study entry.

3. Rapidly progressive, life-threatening metastases, including any of the following:

1. Patients with active parenchymal brain or leptomeningeal involvement

2. Symptomatic lymphangitis carcinomatosis

3. Extensive visceral metastases requiring chemotherapy.

4. Patients with a history of another primary malignancy within 5 years prior to
starting study treatment, except adequately treated basal or squamous cell carcinoma
of the skin, carcinoma in site and the disease under study.

5. More than one prior line of chemotherapy for locally advanced or metastatic disease.

6. AI therapy given in combination with another endocrine agent with the exception of a
GnRH agonist.

7. Radiotherapy to measurable lesion within 2 months of treatment start.

8. Systemic corticosteroids for ≥ 15 days within the last 4 weeks.

9. Evidence of uncontrolled active infection.

10. Evidence of significant medical condition or laboratory finding which, in the opinion
of the Investigator, makes it undesirable for the patient to participate in the
trial.

11. Concurrent therapy with any other investigational agent.

12. Concomitant use within 14 days prior to commencement of study treatment of:

1. Rifampicin and other CYP2C and 3A inducers such as rifabutin, rifapentine,
carbamazepine, phenobarbital, phenytoin and St. John's Wort

2. Systemic carbonic anhydrase inhibitors.

13. Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTcf) >450 ms obtained from 3
electrocardiograms (ECGs)

2. Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g. complete left bundle branch block, third degree heart block

3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years of age or
any concomitant medication known to prolong the QT interval.

14. Uncontrolled abnormalities of serum potassium, sodium, calcium (corrected) phosphate
or magnesium levels.

15. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the formulated investigational medicinal product (IMP) or previous
significant bowel resection that would preclude absorption of Irosustat or the AI.