Inclusion Criteria

        Patients are eligible to be included in the study only if they meet all of the following
        criteria:

          1. Adult women ≥ 18 years of age.

          2. Histologically confirmed HER2-positive breast cancer:

             Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive).

             IHC 3+ or FISH/CISH positive on diagnostic breast biopsy or surgical breast resection
             sample or metastatic disease site biopsy.

          3. Recurrent incurable or metastatic breast cancer:

             Eligible recurrent disease is recurrent disease that is considered incurable by the
             treating oncologist. Many local-only recurrences are treated with curative intent; a
             treatment plan with curative intent for a local-only recurrence would indicate that
             the patient is not eligible for this clinical trial. A local-only recurrence must be
             considered incurable by the treating oncologist for the patient to be eligible.

          4. At least one measurable lesion according to RECIST criteria (Version 1.1). Patients
             with bone only disease are not eligible.

          5. Patient has received at least one trastuzumab-based or T-DM1-based treatment regimen
             in the setting of metastatic disease or incurable locoregional recurrence. A
             trastuzumab-based or T-DM1-based treatment regimen is considered as any treatment
             regimen that includes trastuzumab or T-DM1.

             Patients must have had at least 1 line of therapy for metastatic and/or incurable
             locoregional recurrent disease to be eligible. A patient is eligible regardless of the
             period of time from adjuvant therapy so long as she has disease that is progressing
             after at least 1 line of trastuzumab-based therapy in the setting of metastatic
             disease and/or incurable locoregional recurrence.

          6. Disease progression during or following at least 1 prior trastuzumab-based or
             trastuzumab emtansine (T-DM1) based treatment regimen in the setting of metastatic
             disease or incurable locoregional recurrence.

          7. ECOG performance status ≤ 2.

          8. Life expectancy of at least 3 months.

          9. Availability of fresh tissue and/or archival tumour tissue at screening.

         10. Women of childbearing potential must agree to use a highly effective method of
             contraception when sexually active. This applies from signing of the informed consent
             form until at least 100 days after the last study drug administration. The
             investigator or a designated associate is required to advise the patient how to
             achieve an adequate birth control. Highly effective contraception is defined in the
             study as methods that achieve a failure rate of less than 1% per year when used
             consistently and correctly. Such methods include:

             i. Combined (oestrogen and progestogen containing) hormonal contraception associated
             with inhibition of ovulation (oral, intravaginal, transdermal).

             ii. Progestogen-only hormonal contraception associated with inhibition of ovulation
             (oral, injectable and implantable).

             iii. Intrauterine device (IUD).

             iv. Intrauterine hormone-releasing system (IUS).

             v. Bilateral tubal occlusion.

             vi. Successfully vasectomised partner.

             vii. Sexual abstinence.

         11. Adequate baseline laboratory values collected no more than 14 days before starting
             study treatment:

             Total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with metastatic disease in the
             liver).

             Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x
             ULN for patients with liver involvement from breast cancer).

             Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of
             Diet in Renal Disease (MDRD) abbreviated formula. If not on target, this evaluation
             may be repeated once after at least 24 hours either according to the MDRD abbreviated
             formula or by 24 hour sampling. If the later result is within acceptable range, it may
             be used to fulfil the inclusion criteria instead.

             International normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x
             ULN. Patients who are therapeutically treated with an agent such as warfarin or
             heparin will be allowed to participate provided that no prior underlying coagulopathy
             disorder. Close monitoring of these patients (Day 15 of Cycle 1 and Day 1 of each
             cycle) will be performed until INR/PTT is stable based on a measurement that is pre-
             dose as defined by the local standard of care.

             Platelet count ≥ 75 x 109/L. For patients with breast cancer bone marrow infiltration,
             platelet count ≥ 50 x 109/L.

             Haemoglobin (Hb) ≥ 8 g/dL.

             Absolute neutrophil count (ANC) ≥ 1 x 109/L. For patients with malignant bone marrow
             infiltration, ANC count ≥ 0.75 x 109/L.

             Fasting blood glucose ≤ 6.0 mmol/L if not diabetic or ≤ 8.9 mmol/L if diabetic.

         12. Left ventricular ejection fraction (LVEF), at or above the Institutions lower limit of
             normal, as determined by ECHO or MUGA.

         13. Patients must have recovered from clinically significant side effects associated with
             prior radiotherapy and chemotherapy with the exception of fatigue or neuropathy.

        Exclusion criteria

        Patients who meet any of the following criteria at the time of screening will be excluded
        from study registration:

          1. Known breast cancer involvement of the brain, unless adequately controlled based on
             the clinical judgement of the treating physician.

          2. Congestive heart failure > New York Heart Association (NYHA) class II.

          3. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months). Myocardial infarction less than 6 months before registration.

          4. Uncontrolled arterial hypertension despite optimal medical management (per
             investigator's opinion).

          5. Uncontrolled Type I or II diabetes mellitus. Defined as HbA1c > 8.5% as determined
             during screening laboratory assessments.

          6. Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 3 months before registration.

          7. Non-healing wound, ulcer, or bone fracture.

          8. Active, clinically serious infections > CTCAE Grade 2 (CTCAE v4.0).

          9. Known history of human immunodeficiency virus (HIV) infection.

         10. Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV
             up to 28 days prior to study drug start using the routine hepatitis virus laboratory
             panel. Patients who test positive for Hepatitis B surface Antigen (HBsAg) or Hepatitis
             B core Antibody (HBcAb) will be eligible if they are negative for HBV-DNA; patients
             who test positive for anti-HCV antibody will be eligible if they are negative for HCV-
             RNA.

         11. Patients with CMV PCR positive.

         12. Patients with seizure disorder requiring medication.

         13. Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding
             event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study treatment.

         14. Proteinuria of Grade 3 or higher (CTCAE v4.0). Patient will be excluded if > 2+ on
             urinalysis (unless 24hr collection shows 24 hour urinary protein < 3.5g/24hrs).

         15. History or concurrent condition of interstitial lung disease of any severity, and/or
             severely impaired lung function (as judged by the investigator).

         16. Concurrent diagnosis of pheochromocytoma.

         17. Pregnant or breast-feeding patients. Women of childbearing potential must have a serum
             or urine pregnancy test performed a maximum of 7 days before start of treatment, and a
             negative result must be documented before start of treatment.

         18. Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior
             therapy/procedure, excluding alopecia, peripheral neuropathy, and bone marrow
             parameters.

         19. Known hypersensitivity to any of the test drugs, test drug classes, or excipients in
             the formulation.

         20. Substance abuse, medical, psychological or social conditions that may interfere with
             the patient's participation in the study or evaluation of the study results.

         21. Any illness or medical conditions that are unstable or could jeopardize the safety of
             patients and their compliance in the study.

         22. Patients permanently withdrawn from study participation will not be allowed to re-
             enter the study.

             Excluded previous therapies and medications:

         23. Treatment with investigational drugs other than PI3K inhibitors less than 28 days
             before start of treatment.

         24. Ongoing immunosuppressive therapy.

         25. Radiotherapy or immuno-/chemotherapy less than 4 weeks (28 days) before start of
             treatment.

         26. Myeloid growth factors less than 7 days before start of treatment.

         27. Blood or platelet transfusion less than 7 days before start of treatment.

         28. Ongoing systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone
             or equivalent. Previous corticosteroid therapy must be stopped or reduced to the
             allowed dose 7 days before performing the screening CT scan (or PET-CT/MRI as per
             RECIST 1.1) and again prior to the first study drug administration. If a patient is on
             chronic corticosteroid therapy, corticosteroids should be de-escalated to the minimum
             allowed dose before the screening. Patients may continue to use topical or inhaled
             corticosteroids.

         29. History of having received an allogeneic bone marrow or organ transplant.

         30. Major surgical procedure or significant traumatic injury (as judged by the
             investigator) less than 28 days before start of treatment. This does not include the
             study-specific biopsy.

         31. Anti-arrhythmic therapy (beta blockers or digoxin are permitted).

         32. Use of strong inhibitors of CYP3A4 is prohibited from Day -14 of Cycle 1 until the
             Safety follow up visit.

         33. Use of inducers of CYP3A4 is prohibited from Day -14 of Cycle 1 until the Safety
             follow up visit.

        Zoledronate or denosumab for patients with bone metastasis is allowed.