Cardiac Side Effects of Systemic Therapy in Early-Stage Breast Cancer

NCT07588425 | Not Yet Recruiting

• 1 other identifier: GUTF-MO-OnkoKard-2026-01
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to evaluate cardiac side effects in women with early-stage breast cancer who receive systemic chemotherapy and/or anti-HER2 therapy as part of their standard cancer care. The main questions it aims to answer are: Can changes in Global Longitudinal Strain (GLS) on echocardiography detect early cardiac dysfunction before a drop in left ventricular ejection fraction (LVEF) becomes apparent? Are changes in circulating microRNA levels in the blood associated with early cardiac dysfunction during cancer treatment? Does cardiac dysfunction occur more frequently with anthracycline-containing chemotherapy compared to anthracycline-free regimens? Participants already receiving standard chemotherapy and/or anti-HER2 therapy as part of their routine cancer care will undergo echocardiography (LVEF and GLS), provide blood samples for microRNA analysis, and complete quality of life questionnaires at four time points: before treatment (baseline), and at 3, 6, and 12 months after starting treatment.

Conditions

Breast Cancer (Early Breast Cancer); Cardiotoxicity; Cancer Therapy-Related Cardiac Dysfunction

Keywords

Early-stage breast cancer; Anthracyclines; Anti-HER2 therapy; Cardiotoxicity; GLS; microRNA; Cardio-oncology

Outcome Measures

Primary Outcomes (1)

• Incidence of cancer therapy-related cardiac dysfunction (CTRCD)

  CTRCD defined per ESC 2022 Cardio-Oncology Guidelines as: an absolute LVEF reduction of ≥10 percentage points to a value below 53%, AND/OR a relative reduction in GLS of ≥15% from baseline. LVEF is measured by transthoracic echocardiography using Simpson's biplane method; GLS is measured by speckle-tracking analysis using a standardized protocol.

  From baseline through Month 12

Secondary Outcomes (11)

• Change from baseline in Left Ventricular Ejection Fraction (LVEF)

  Baseline, Month 3, Month 6, Month 12

• Change from baseline in Global Longitudinal Strain (GLS)

  Baseline, Month 3, Month 6, Month 12

• Change in circulating microRNA expression and association with cardiac function

  Baseline, Month 3, Month 6, Month 12

• Comparison of CTRCD incidence between anthracycline-containing and anthracycline-free regimens

  From baseline through Month 12

• Change from baseline in health-related quality of life: EORTC QLQ-C30

  Baseline, Month 3, Month 6, Month 12

Study Arms (1)

Early-stage breast cancer patients receiving systemic therapy

Adult women with histologically confirmed Stage I-III breast cancer for whom neoadjuvant or adjuvant chemotherapy and/or HER2-targeted systemic therapy is planned, with baseline left ventricular ejection fraction ≥ 50%. Patients receive standard-of-care systemic therapy as determined by their treating oncologist; the study does not modify treatment selection, dose, or duration. For analytic purposes, patients are sub-grouped by chemotherapy regimen (anthracycline-containing vs. anthracycline-free) for comparative analyses of cardiac function and circulating microRNA changes.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult women with histologically confirmed Stage I-III breast cancer for whom neoadjuvant or adjuvant systemic therapy (chemotherapy and/or HER2-targeted therapy) is planned, recruited from the Medical Oncology outpatient clinic at Gazi University Faculty of Medicine Hospital, Ankara, Türkiye.

You may qualify if:

• Histologically confirmed diagnosis of breast cancer
• Stage I, II, or III disease
• Planned neoadjuvant or adjuvant chemotherapy and/or HER2-targeted systemic therapy
• Baseline transthoracic echocardiographic left ventricular ejection fraction (LVEF) ≥ 50%
• Age ≥ 18 years
• Able and willing to provide written informed consent

You may not qualify if:

• Metastatic (Stage IV) breast cancer
• Pre-existing heart failure or clinically significant cardiac disease
• Prior exposure to chemotherapy or other cardiotoxic systemic therapy
• Concurrent active malignancy other than breast cancer
• Inability or unwillingness to comply with the planned follow-up and assessment schedule

Sponsors & Collaborators

• Fatih GURLER: lead

Study Sites (1)

Gazi University Faculty of Medicine

Ankara, Ankara, 06560, Turkey (Türkiye)

Location

Related Publications (6)

• Lyon AR, Lopez-Fernandez T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, Cutter DJ, de Azambuja E, de Boer RA, Dent SF, Farmakis D, Gevaert SA, Gorog DA, Herrmann J, Lenihan D, Moslehi J, Moura B, Salinger SS, Stephens R, Suter TM, Szmit S, Tamargo J, Thavendiranathan P, Tocchetti CG, van der Meer P, van der Pal HJH; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022 Nov 1;43(41):4229-4361. doi: 10.1093/eurheartj/ehac244. No abstract available.

  PMID: 36017568 RESULT

• Kuang Z, Ge Y, Cao L, Wang X, Liu K, Wang J, Zhu X, Wu M, Li J. Precision Treatment of Anthracycline-Induced Cardiotoxicity: An Updated Review. Curr Treat Options Oncol. 2024 Aug;25(8):1038-1054. doi: 10.1007/s11864-024-01238-9. Epub 2024 Jul 27.

  PMID: 39066853 RESULT

• Poovorawan N, Susiriwatananont T, Teerapakpinyo C, Chariyavilaskul P, Sitthideatphaiboon P, Jarutasnangkul L, Tumkosit M, Chattranukulchai P, Theerasuwipakorn N, Aporntewan C, Shuangshoti S, Manasnayakorn S, Vinayanuwattikun C, Vorasettakarnkij Y, Sriuranpong V. Long-term impact of anthracycline in early-stage breast cancer, bridging of MiRNAs profiler for early cardiotoxicity. Cardiooncology. 2025 Apr 23;11(1):39. doi: 10.1186/s40959-025-00337-2.

  PMID: 40270054 RESULT

• Boen HM, Cherubin M, Franssen C, Gevaert AB, Witvrouwen I, Bosman M, Guns PJ, Heidbuchel H, Loeys B, Alaerts M, Van Craenenbroeck EM. Circulating MicroRNA as Biomarkers of Anthracycline-Induced Cardiotoxicity: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2024 Feb 27;6(2):183-199. doi: 10.1016/j.jaccao.2023.12.009. eCollection 2024 Apr.

  PMID: 38774014 RESULT

• Mecinaj A, Gulati G, Ree AH, Gravdehaug B, Rosjo H, Steine K, Wisloff T, Geisler J, Omland T, Heck SL. Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction. JACC CardioOncol. 2024 Jan 16;6(1):83-95. doi: 10.1016/j.jaccao.2023.10.008. eCollection 2024 Feb.

  PMID: 38510299 RESULT

• Bernasconi R, Kuster GM. Non-coding RNAs and their potential exploitation in cancer therapy-related cardiotoxicity. Br J Pharmacol. 2025 Jan;182(2):296-315. doi: 10.1111/bph.16416. Epub 2024 May 27.

  PMID: 38802331 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral venous whole blood samples are collected in EDTA tubes at four time points (baseline, Month 3, Month 6, and Month 12). Total nucleic acid is isolated from whole blood for downstream quantitative analysis of circulating microRNAs (miR-34a, miR-146a, miR-21, miR-155, miR-1, miR-133a, miR-208a, and miR-499) by reverse transcription quantitative real-time PCR. Samples are stored at -80°C at the Department of Medical Biology, Gazi University Faculty of Medicine, until analysis. Samples are used solely for the purposes of this study and will be destroyed upon study completion in accordance with applicable regulations.

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• Fatih Gürler

  Gazi University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sıla Soylu Koçoğlu, MD

CONTACT

+905012735223; drsilasoylu@gmail.com

Fatih Gürler, MD

CONTACT

+905325495597; drfatihgurler@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2026
• First Posted: May 14, 2026
• Study Start: May 10, 2026
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

TU (1)