Can Dapagliflozin Prevent Heart Failure in Breast Cancer Patients After Treatment?
While dapagliflozin has not been specifically studied in breast cancer survivors for heart failure prevention, emerging preclinical evidence and an ongoing clinical trial (PROTECT) suggest potential cardioprotective benefits against anthracycline-induced cardiotoxicity, though current guideline-based recommendations for SGLT2 inhibitors in heart failure prevention apply primarily to patients with diabetes and established cardiovascular risk.
Current Evidence Landscape
Established Benefits in General Populations
SGLT2 inhibitors, including dapagliflozin, demonstrate robust heart failure prevention benefits in patients with type 2 diabetes and cardiovascular disease or risk factors, with a 27% reduction in heart failure hospitalizations in the DECLARE-TIMI 58 trial 1.
The FDA-approved indication for dapagliflozin includes reducing cardiovascular death and heart failure hospitalization in adults with heart failure (both reduced and preserved ejection fraction), regardless of diabetes status 2.
In the DAPA-HF trial, dapagliflozin reduced the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85), with consistent benefits in patients with and without diabetes 1, 3.
Specific Evidence for Breast Cancer Populations
Preclinical data strongly support cardioprotective effects against anthracycline toxicity:
In mouse models of doxorubicin cardiotoxicity, dapagliflozin prevented ejection fraction reduction and reduced myocardial NF-κB expression, systemic inflammatory biomarkers (IL-1β, IL-6, TNF-α), and cardiac injury markers (troponin-T, BNP, NT-pro-BNP) 4.
Dapagliflozin demonstrated cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to doxorubicin by reducing intracellular ATP and calcium levels, lipid peroxidation, and NLRP-3 expression 4.
Clinical trial evidence is emerging:
The PROTECT trial (NCT06341842) is the first randomized clinical study designed to evaluate whether dapagliflozin can reduce anthracycline- and/or trastuzumab-associated cardiotoxicity in patients with early-stage breast cancer 5.
This ongoing trial is enrolling chemotherapy-naive patients (18-70 years) with stage I-III breast cancer scheduled for anthracycline ± trastuzumab treatment, randomizing them to dapagliflozin 10 mg daily versus standard of care 5.
Clinical Decision Algorithm
For Breast Cancer Patients WITH Diabetes or Established Heart Failure
Strongly recommend dapagliflozin 10 mg daily:
Patients with type 2 diabetes and history of breast cancer treatment who have cardiovascular disease or risk factors should receive SGLT2 inhibitors to prevent heart failure hospitalization 1.
Patients who have already developed heart failure (LVEF ≤40% or >40% with symptoms) should receive dapagliflozin regardless of diabetes status, as this is an FDA-approved indication with proven mortality and morbidity benefits 2, 3.
For Breast Cancer Patients WITHOUT Diabetes or Established Heart Failure
Current evidence does not support routine prophylactic use, but consider in high-risk scenarios:
No guideline-based recommendation exists for SGLT2 inhibitors in non-diabetic, non-heart failure patients solely based on cancer treatment history 1.
However, patients treated with anthracyclines (especially doxorubicin) ± trastuzumab represent a high-risk population for cardiotoxicity, and enrollment in clinical trials like PROTECT should be considered 5.
Monitor for early signs of cardiac dysfunction (reduced ejection fraction, elevated NT-pro-BNP, troponin) and initiate dapagliflozin if asymptomatic left ventricular dysfunction (stage B heart failure) develops 1.
Important Clinical Considerations
Mechanism of Cardioprotection in Cancer Patients
SGLT2 inhibitors reduce systemic inflammation, oxidative stress, and myocardial fibrosis—mechanisms directly relevant to anthracycline cardiotoxicity 4.
The cardioprotective effects appear independent of glucose-lowering, as benefits are consistent in non-diabetic populations 6, 7.
Safety Profile
Common adverse effects include genital mycotic infections (1.5-1.7%) and urinary tract infections (2.3-2.7%), which are generally manageable 3.
Hypotension may occur in approximately 5.7% of patients, particularly those with volume depletion 3.
Diabetic ketoacidosis risk is significantly lower in non-diabetic populations 3.
Monitoring Strategy
For patients initiated on dapagliflozin after breast cancer treatment:
Baseline and periodic echocardiography to assess ejection fraction and cardiac function 5.
Serial measurement of cardiac biomarkers (NT-pro-BNP, high-sensitivity troponin) at 3,6,12, and 18 months 5.
Monitor renal function (eGFR) periodically; dapagliflozin can be used with eGFR as low as 20-30 mL/min/1.73m² 3, 2.
Assess for signs of volume depletion, particularly in patients on diuretics 3.
Critical Caveats
The evidence gap is significant: While preclinical data are compelling and the PROTECT trial is ongoing, no completed randomized controlled trial has specifically evaluated dapagliflozin for primary prevention of heart failure in breast cancer survivors without diabetes or established cardiovascular disease 5.
Anthracycline exposure creates a unique risk profile: Sequential therapy with anthracyclines and HER-2 blocking agents (trastuzumab) is associated with higher cardiotoxicity risk compared to monotherapy, potentially justifying more aggressive prevention strategies 5.
Current practice should prioritize established indications: Until PROTECT trial results are available, dapagliflozin should be prescribed based on FDA-approved indications (diabetes with cardiovascular risk, established heart failure, or chronic kidney disease) rather than cancer treatment history alone 2.