Breast Cancer
Conditions
Brief summary
Background: Breast cancer is the most frequently diagnosed malignancy among women worldwide and a major cause of morbidity and mortality. Anthracycline-based chemotherapy, particularly doxorubicin, remains a cornerstone of treatment; however, its clinical utility is limited by dose-dependent cardiotoxicity that can lead to irreversible cardiac dysfunction and heart failure. The search for effective cardioprotective interventions is therefore a key priority in cardio-oncology. Aim: This study aims to compare the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing doxorubicin-induced cardiotoxicity in Egyptian women with breast cancer. Methods: A prospective, randomized, controlled clinical trial will be conducted at Oncology Hospital of Tanta University. Eligible adult female patients with histologically confirmed breast cancer scheduled to receive anthracycline-containing chemotherapy will be randomized into three groups: (1) control (standard care), (2) SGLT2 inhibitor group (dapagliflozin 10-25 mg daily), and (3) DPP-4 inhibitor group (sitagliptin 50-100 mg daily). Treatment will start five days before the first chemotherapy cycle and continue for six months, with follow-up for an additional six months. Cardiac function will be assessed by echocardiography (LVEF and GLS) and biomarkers (Cardiac Troponin T, and NT-proBNP). The primary endpoint is the incidence of cardiotoxicity defined by a ≥10% decline in LVEF to \<50% or a \>15% relative decline in GLS accompanied by biomarker elevation. Expected Outcomes: It is anticipated that both SGLT2 and DPP-4 inhibitors will reduce the incidence and severity of doxorubicin-induced cardiotoxicity, with SGLT2 inhibitors expected to demonstrate superior cardioprotective efficacy. Findings from this study may support the integration of cardioprotective antidiabetic agents into oncology care pathways to improve the cardiac outcomes and overall survival of breast cancer patients.
Interventions
Dapagliflozin 10 mg orally once daily (dose may increase to 25 mg if tolerated after Cycle 1) starting ≥5 days before first DOX dose and continued for 3 months.
Sitagliptin 100 mg orally once daily (50 mg if eGFR 30-45 mL/min/1.73m²) starting ≥5 days before first DOX dose and continued for 3 months.
OTHERStandard Care (in control arm)
Usual care without prophylactic cardioprotective agent (guideline directed initiation permitted if clinically indicated post randomization; recorded and adjusted for).
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Interventional, prospective, randomized, parallel controlled clinical trial
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
1. Female, ≥18 years, Egyptian nationality. 2. Breast cancer (any stage) with planned anthracycline containing chemotherapy (intended cumulative DOX ≥240 mg/m² or epirubicin ≥360 mg/m² equivalents). 3. Baseline echo suitable for LVEF ≥53%. 4. Able to consent and comply with follow up.
Exclusion criteria
* • Type 1 and type 2 diabetes; history of diabetic ketoacidosis; pregnancy/lactation. * Symptomatic HF, cardiomyopathy, significant valvular disease, prior anthracycline exposure. * Baseline hypotension (SBP \<95 mmHg), recurrent UTIs/mycotic infections, active foot ulcer/critical limb ischemia. * Inflammatory diseases, liver and kidney diseases. * Autoimmune diseases. * Other type of malignancies or metastatic diseases. * Patients who exposed to surgery less than one month. * Concomitant dexrazoxane planned upfront (allowed only for rescue; documented). * Known hypersensitivity to study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants experiencing cardiotoxicity | Within 3 months from initiation of therapy. | Cardiotoxicity will be defined as the occurrence of any of the following during the study period: A decline in left ventricular ejection fraction (LVEF) ≥ 10% from baseline resulting in an LVEF \< 50%, as measured by echocardiography, or A relative reduction in global longitudinal strain (GLS) \> 15% from baseline, as assessed by speckle-tracking echocardiography. Unit of Measure: Percentage of participants experiencing cardiotoxicity (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Left Ventricular Ejection Fraction (LVEF) | 3 months | Description: Absolute change in left ventricular ejection fraction from baseline to 3 months, measured by transthoracic echocardiography. Unit of Measure: Percentage points (%) |
| Percentage Change in Global Longitudinal Strain (GLS) | 6 months | Description: Relative percentage change in global longitudinal strain from baseline to 3 months, assessed using speckle-tracking echocardiography. Unit of Measure: Percentage (%) |
| Time to cardiotoxicity and HF hospitalization through 6 months. | 6 months | — |
| Change in serum cardiac biomarker levels e.g., troponin | 3 months | Change in Cardiac Biomarkers (if applicable) Description: Change in serum cardiac biomarker levels (e.g., troponin) from baseline to 3 months. Troponin: ng/L |
| Change in serum cardiac biomarker levels (e.g., NT-proBNP) | 3 months | Description: Change in serum cardiac biomarker levels (e.g., NT-proBNP) from baseline to 3 months. NT-proBNP: pg/mL |
| All cause mortality and cancer therapy interruptions due to cardiac reasons. | 6 months | — |
Contacts
CONTACTMai Aboelyazed Elgebaly, Associate Lecturer
PRINCIPAL_INVESTIGATORMohamed Abdelhamid Almeldein, Professor
Tanta University
PRINCIPAL_INVESTIGATORMohamed Elhussieny Shams, Professor
Mansoura University
STUDY_DIRECTORHaidy Mahmoud Sami, Lecturer
Delta University
STUDY_DIRECTOROsama Hamid Shoaeb, Associate Professor
Tanta University
Outcome results
None listed