Sodium-glucose Transporter Type 2 Inhibition in Anthracycline-related Cardiotoxicity

Cardiotoxicity is heart damage that arises from certain drugs, such as those used for cancer treatment and develops in approximately 10% of patients with breast cancer who are treated with anthracyclines. It has been suggested that sodium-glucose transporter-2 (SGLT2) inhibitors may reduce the damage to the heart caused by anthracycline chemotherapy. The investigators wish to determine whether dapagliflozin (SGLT2 inhibitor) taken daily during chemotherapy will reduce the rate of cardiotoxicity.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* Patients with breast cancer between 18-70 years of age.
* Patients with low to medium cardiovascular risk.
* Patients scheduled for adjuvant or neo-adjuvant anthracycline therapy.
* Patients who are able to give written informed consent to take part in the study.
* Patients who can read and understand English.

The current thresholds for defining cardiovascular risk for patients undergoing anthracycline chemotherapy are as follows: normal resting 12-lead electrocardiogram, plasma cardiac troponin I concentration \< 99th centile, serum brain natriuretic peptide concentration \<35 pg/mL or serum N-terminal pro-brain natriuretic peptide concentration \<125 pg/mL, left ventricular ejection fraction \>55%, global longitudinal strain \>-18% and healthy life-style (normal body-mass index, non-smoker). Low cardiovascular risk will allow for the presence of one abnormal life-style factor (body-mass index indicating obesity (\>30 kg/m2), current smoker or significant smoking history), or presence of only one of the following in the clinical history: hypertension, stage 1-2 chronic kidney disease, age 65-79 years, borderline left ventricular ejection fraction (50-54%) or elevated cardiac biomarkers. Medium cardiovascular risk will permit the combination of any 2-4 of the lifestyle or clinical history variables indicated above.

Exclusion Criteria:

* Patients with a known intolerance of dapagliflozin
* Patients with high cardiovascular risk as specified by the most recent cardio-oncology guidelines.
* Patients with significant renal impairment (estimated glomerular filtration rate \<45 mL/min/1.73 m2).
* Patients with a previous cancer diagnosis.
* Patients with known type 1 or 2 diabetes mellitus. We will not actively screen for diabetes. This is not done in clinical practice and there have been no issues.
* Patients with a contraindication to magnetic resonance imaging.
* Patients with prior exposure to anthracyclines.
* Patients who cannot read and understand English.
* Patients who are pregnant

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