Evaluation of cardiac markers in patients with breast cancer receiving antineoplastic treatment: a systematic review
Review Article

Evaluation of cardiac markers in patients with breast cancer receiving antineoplastic treatment: a systematic review

Tiago Nunes da Silva Soares1 ORCID logo, Thaís Moura Gascón2 ORCID logo, Fernando Luiz Affonso Fonseca2,3 ORCID logo, Neif Murad4 ORCID logo, Samantha Sanches de Carvalho2 ORCID logo, Glaucia Luciano da Veiga2 ORCID logo, Beatriz da Costa Aguiar Alves2 ORCID logo, Edimar Cristiano Pereira3 ORCID logo

1Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo/Federal University of São Paulo, UNIFESP – Diadema Campus, São Paulo, Brazil; 2Clinical Laboratory Analysis of ABC Medical School, Santo André, São Paulo, Brazil; 3Department of Pharmaceutical Sciences, Federal University of São Paulo/UNIFESP, Diadema Campus, São Paulo, Brazil; 4Department of Cardiovascular of ABC Medical School, Santo André, São Paulo, Brazil

Contributions: (I) Conception and design: TN da Silva Soares, FLA Fonseca; (II) Administrative support: EC Pereira, TN da Silva Soares; (III) Provision of study materials or patients: FLA Fonseca, TM Gascón; (IV) Collection and assembly of data: SS de Carvalho, TM Gascón; (V) Data analysis and interpretation: GLD Veiga, BDCA Alves; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Thaís Moura Gascón, PhD. Clinical Laboratory Analysis of ABC Medical School, Av. Lauro Gomes, 2000, Bairro Sacadura Cabral, Santo André, ZIP Code 09060-870, São Paulo, Brazil. Email: tmoura46@gmail.com.

Background: Cardiac markers are important in the diagnosis of heart and coronary insufficiency, it is through them that they can measure the damage to cardiac fibers resulting from these diseases. Recent research has shown that the levels of biomarkers are altered who have neoplasms under chemotherapy treatment without these patients having any clinical manifestations. The research was to conduct a systematic review of the main cardiac biomolecular markers in scientific publications bases and to verify how their levels present in individuals with breast cancer, as well as to analyze the influence of antineoplastic treatment in the circular levels of these markers resulting from the effects of cardiac damage on patient therapy and which are good predictors of cardiovascular diseases related to chemotherapy treatment.

Methods: Medline, Lilacs and Cochrane and in these databases, systematic searches of publications were carried out between the years 2010 and 2020 using the descriptors “Mesh” or the equivalent in the chosen database. Studies that evaluated the following cardiac biomarkers: troponin, pro-type B natriuretic peptide (proBNP)/N-terminal pro-BNP (NT-proBNP), myoglobin, creatine kinase-MB fraction, fibrinogen, and D-dimer.

Results: At the end, 31 published articles were obtained for analysis in which cardiac markers ultra-sensitive troponin I and T, myoglobin, and NT-proBNP showed to be the best predictors of cardiotoxicity for breast cancer patient under chemotherapy.

Conclusions: The ultra-sensitive cardiac markers troponin I and T, NT-proBNP and myoglobin, were the ones that provided the best biomarkers in detecting cardiotoxicity, requiring continuous research and research for cardiotoxic biomarkers.

Keywords: Cardiac markers; breast cancer; chemotherapy; cardiotoxicity; biomarkers

Submitted Dec 20, 2024. Accepted for publication Oct 22, 2025. Published online Dec 22, 2025.

doi: 10.21037/cco-24-136

Highlight box

Key findings

• Ultra-sensitive troponin I and T, N-terminal pro-type B natriuretic peptide, and myoglobin were identified as the best biomarker predictors of cardiotoxicity in breast cancer patients undergoing chemotherapy.

What is known and what is new?

• It is known that chemotherapy can cause cardiac damage; however, this systematic study confirms elevated cardiac biomarker levels even in the absence of clinical manifestations in patients with neoplasms.

What is the implication, and what should change now?

• The results highlight the need for continuous monitoring of these biomarker levels in patients undergoing chemotherapy. This will enable early detection of cardiac damage, improve clinical intervention, and reduce long-term cardiovascular risks.

Introduction

Background

Cardiac biomarkers play a fundamental role in the diagnosis of cardiac damage. Recent studies indicate the relevance in detecting cardiotoxicity induced by chemotherapy in the treatment of breast cancer, being seen as good predictor of cardiovascular diseases in patients.

Rationale and knowledge gap

Although chemotherapy is known to cause cardiac damage, studies specifically identifying reliable biomarkers for early cardiotoxicity remain limited. This study aims to systematically evaluate cardiac biomarkers to address this gap and propose reliable predictors for clinical practice.

Objective

The research was to conduct a systematic review of the main cardiac biomolecular markers in scientific publications bases and to verify how their levels present in individuals with breast cancer, as well as to analyze the influence of antineoplastic treatment in the circular levels of these markers resulting from the effects of cardiac damage on patient therapy and which are good predictors of cardiovascular diseases related to chemotherapy treatment.

Breast cancer is characterized as the most common neoplasm among women worldwide and in Brazil, being lower in incidence only to non-melanoma skin cancer. Currently, it accounts for about 28% of new cases each year in females. Although rare, it affects 1% of men (1,2). The methods of diagnosis of breast cancer are breast self-exam, clinical breast exam and mammograms that stands out as the only in which its application in screening programs has proven efficacy in reducing mortality. To improve diagnostic accuracy, ultrasound and magnetic resonance imaging (3) are associated. Once suspected, the biopsy will be performed through minor surgery or surgical puncture. The biopsied material will go to the anatomopathological analysis that will give the definitive diagnosis (3,4). To the diagnostic certainty come locoregional or systemic treatments, in consent to staging. This describes cancer’s characteristic: its spread and metastasis to other organs. Staging I or II is reserved for surgery, a conservative or partial or total mastectomy that follows breast reconstruction. The prognosis stems from axillary lymph nodes, and radiotherapy can be considered in some situations. Systemic treatment will be determined according to recurrence, age, lymph node involvement and degree of cell differentiation (5). Tumor characteristics result from the measurement of hormone receptors (estrogenic and progesteronic) that follow hormone therapy while biological therapy is linked to the presence of the HER-2 receptor (4,6). Staging III is reserved for systemic-surgical treatment. At stage IV, the therapeutic decision is balanced between tumor response and survival, considering the potential side effects. Systemic treatment is reserved for this staging, while local treatment is associated with palliative care (6,7).

In decades past the antineoplastic therapies old and current as immunotherapy raises encouragement to patients with malignant neoplasia that follows the highest survival rates that provides opportunities for cardiac damage (8-10). The cardiotoxicity resulting from treatment is of concern during and extends to the survival period, with adverse cardiovascular outcomes aggravated by pre-existing cardiovascular diseases and/or additional cardiovascular risk factors (11-13). The most common forms of cardiotoxicity are manifested with clinical congestive heart failure with reduced ejection fraction (HFrEF), hypertension and arrhythmias. The antineoplastic dosage, age of the patient, previous heart diseases, give rise to a higher risk of cardiotoxicity (14-16). Before and after treatment, cardiac function will be evaluated by Doppler echocardiography and the global longitudinal strain (17-19) is inserted. The use of the aforementioned method does not allow early diagnosis of cardiac dysfunction, thus the insertion of elevations of cardiovascular biomarkers, especially natriuretic peptides (nps) including type B natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), and cardiac troponins (cTn), both high sensitivity (hs) and conventional would detect dysfunction early (20). In this systematic review, the biomarkers used to detect cardiotoxicity in patients with breast cancer under antineoplastic treatment were sought. We present this article in accordance with the PRISMA reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-24-136/rc).

Methods

This systematic review covered publications between 2010 and 2020, with no research protocol being registered. Research was conducted in the PubMed/Medline; Latin American and Caribbean Health Sciences Literature (LILACS) and Cochrane Library databases, studies reporting evaluations of these biomarkers during chemotherapy treatment. The search strategies were carried out using the following descriptors: “Breast Cancer”; “Breast Neoplasms”; “Troponin”; “Natriuretic Peptide Brain”; “Fibrin Fibrinogen Degradation Products”; “Creatine Kinase”; “Myoglobin”; and “Fibrinogen” as in described below according to PICO (Table 1).

Table 1

Combination of descriptors used in the systematic review according to the PICO research question

Combination Descriptors
Population Breast cancer OR Breast neoplasm
Intervention Troponin OR –
Natriuretic peptide brain OR pro-brain natriuretic peptide [1–76] (supplementary concept)
Myoglobin OR –
Fibrin fibrinogen degradation products OR –
Creatine kinase OR –
Fibrinogen–
Control Comparison between markers
Outcome Predictive or not of cardiotoxicity

PICO, Population, Intervention, Control, Outcome.

Inclusion criteria were breast cancer receiving any type of chemotherapy treatment; patients with altered levels of any of the previously selected cardiac markers evaluated during the treatment period; publications that the study design was a clinical assay or prospective study (case-control, cohort, case studies). The exclusion criteria for patients were cancer other than breast cancer, patients who associated chest radiotherapy with chemotherapy, other types of studies and publications that were not available in English, Portuguese, Spanish and cardioprotection studies.

Predictive marker was considered in the studied population, with a statistically significant serum level, regardless of the time of its occurrence.

Results

The search strategy identified 441 records. A total of 240 duplicates, 12 records marked as ineligible by automation tools, and 7 records removed for other reasons were excluded, resulting in 182 records being screened. Of these, 70 were excluded, and 112 reports were assessed for eligibility. Following full-text evaluation, 81 reports were excluded for specific reasons, leaving 31 studies included in the review and qualitative synthesis. Based on the criteria chosen, a flowchart was prepared to illustrate the articles’ selection in this review (Figure 1). Table 2 summarizes data extracted from articles selected for analysis and Table 3 summarizes the data extracted from studies evaluating cardiac markers.

Figure 1 Flowchart of selection and extraction of articles for review.

Table 2

Data extracted from articles selected for analysis

Study Number of participants Mean age (years) Treatment Study design Treatment duration Marker Predictive
Malik et al. 2016 (21) 33 49.4 5-fluorouracil + epirubicin + cyclophosphamide or 5-fluorouracil + epirubicin + cyclophosphamide or doxorubicin/paclitaxel or docetaxel Prospective 6 months Troponin T Yes
NT-proBNP Yes
Advani et al. 2017 (22) 11 51 Doxorubicin Prospective 2 cycles Troponin T* Yes
NT-proBNP Yes
11 60 Trastuzumab 2 cycles Troponin T* No
NT-proBNP Yes
Kittiwarawut et al. 2013 (23) 52 50 Doxorubicin + cyclophosphamide Prospective 9 weeks NT-proBNP Yes
Troponin T No
CK-MB No
Yu et al. 2016 (24) 69 53 Paclitaxel + trastuzumab + pertuzumab Prospective 3–38 months Troponin I No
NT-proBNP No
Tanindi et al. 2011 (25) 37 42 Doxorubicin + cyclophosphamide or doxorubicin + cyclophosphamide + 5-fluorouracil Prospective 45 days NT-proBNP Yes
Demissei et al. 2019 (26) 159 49.2 Doxorubicin + cyclophosphamide/paclitaxel Prospective Up to 3.5 years Troponin T* Yes
NT-proBNP Yes
126 49.6 Trastuzumab + docetaxel or cyclophosphamide or carboplatin Troponin T* Yes
NT-proBNP Yes
29 52.1 Doxorubicin + cyclophosphamide/paclitaxel + trastuzumab Troponin T* Yes
NT-proBNP No
Drafts et al. 2013 (27) 53 50 Doxorubicin or daunorubicin Prospective 6 months Troponin I Yes
BNP No
von Hagens et al. 2019 (28) 13 57 Artesunate Clinical assay Up to 41 months Troponin I No
NT-proBNP No
Zardavas et al. 2017 (29) 452 50 Trastuzumab Prospective 1–2 years Troponin T Yes
Troponin I Yes
NT-proBNP Yes
Matos et al. 2016 (30) 92 53.6 Trastuzumab Prospective 12 months NT-proBNP No
De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months NT-proBNP Yes
Troponin T Yes
Troponin I Yes
CK-MB Yes
Myoglobin Yes
40 Anthracyclines + taxanes + tratuzumab 12 months NT-proBNP Yes
Troponin T Yes
Troponin I Yes
CK-MB Yes
Myoglobin Yes
Chen et al. 2024 (32) 73 46 Anthracycline based chemotherapy (epirubicin + cyclophosphamide) Prospective 6 months NT-proBNP + troponin T, CK-MB, myoglobin Yes
Huang et al. 2018 (33) 126 53 Doxorubicin or trastuzumab or doxorubicin + trastuzumab Prospective 6 months BNP Yes
Sawaya et al. 2012 (34) 81 50 Doxorubicin or epirubicin/paclitaxel + trastuzumab/trastuzumab Prospective 15 months Troponin I* Yes
NT-proBNP No
Sawaya et al. 2011 (35) 43 47 Anthracyclines + trastuzumab Prospective 6 months Troponin I* Yes
NT-proBNP No
Kitayama 2017 (36) 40 – Epirubicin + cyclophosphamide + 5-fluorouracil or trastuzumab or epirubicin + cyclophosphamide + 5-fluorouracil + tratuzumab Prospective Up to 18 months Troponin T* Yes
BNP No
Putt et al. 2015 (37) 78 49 Doxorubicin/paclitaxel + trastuzumab/trastuzumab Prospective Up to 15 months Troponin I* Yes
NT-proBNP No
Feola et al. 2011 (38) 53 55 Epirubicin + cyclophosphamide + 5-fluorouracil Prospective 2 years Troponin I Yes
BNP Yes
Inanc et al. 2016 (39) 58 51 Doxorubicin + cyclophosphamide or docetaxel + doxorubicin + cyclophosphamide or 5-fluorouracil + epirubicin or 5-fluorouracil + epirubicin + cyclophosphamide Prospective 21 days Troponin I* Yes
Şendur et al. 2015 (40) 164 49 Trastuzumab Prospective 9/52 weeks CK-MB No
NT-proBNP Yes
Troponin I No
Troponin T* No
Fallah-Rad et al. 2011 (41) 42 47 Trastuzumab Prospective 1 year Troponin T No
NT-proBNP No
Ponde et al. 2018 (42) 172 50 Lapatinib or trastuzumab or lapatinib + trastuzumab Clinical Trial 2 weeks Troponin T No
2 weeks NT-proBNP No
173 18 weeks Troponin T No
18 weeks NT-proBNP No
Morris et al. 2011 (43) 95 46 Doxorubicin + cyclophosphamide/paclitaxel + trastuzumab + lapatinib/trastuzumab + lapatinib Prospective 18 months Troponin I Yes
Veronese et al. 2018 (44) 23 50 Doxorubicin + cyclophosphamide/paclitaxel Prospective 8 months Troponin I Yes
BNP No
Frères et al. 2018 (45) 45 49 Cyclophosphamide + epirubicin/paclitaxel ± trastuzumab or lapatinib Prospective 3 months Troponin T Yes
NT-proBNP Yes
Yang et al. 2012 (46) 4 41 Epirubicin Clinical Trial 4 months Troponin T Yes
CK-MB Yes
Myoglobin Yes
9 4 months Troponin T No
CK-MB No
Myoglobin No
Goel et al. 2012 (47) 36 52 Trastuzumab Prospective 3 weeks Troponin T No
NT-proBNP Yes
Romano et al. 2012 (48) 71 54 Doxorubicin + docetaxel or epirubicin + cyclophosphamide + 5-fluorouracil Prospective 6 cycles Troponin I No
NT-proBNP Yes
Dhir et al. 2019 (49) 41 51.7 Trastuzumab Prospective 12 months Troponin I* No
NT-proBNP Yes
van Boxtel et al. 2015 (50) 55 52.8 Docetaxel + doxorubicin + cyclophosphamide Prospective 1 year Troponin I No
NT-proBNP Yes
Ürun et al. 2015 (51) – 48.5 Trastuzumab Prospective 52 weeks NT-proBNP Yes

*, use of high-sensitivity assay. BNP, brain natriuretic peptide; CK-MB, creatine kinase-MB fraction; NT-proBNP, N-terminal brain natriuretic peptide.

Table 3

Data extracted from studies evaluating cardiac markers

Author Number of participants Mean age (years) Treatment Study design Duration of treatment Marker Predictive
Data extracted from studies evaluating the cardiac marker BNP
   Drafts et al. 2013 (27) 53 50 Doxorubicin or daunorubicin Prospective 6 months BNP No
   Huang et al. 2018 (33) 126 53 Doxorubicin or trastuzumab or dxorubicin + trastuzumab Prospective 6 months BNP Yes
   Kitayama et al. 2017 (36) 40 – Epirubicin + cyclophosphamide + 5-fluorouracil or trastuzumab or epirubicin + cyclophosphamide + 5-fluorouracil + tratuzumab Prospective Up to 18 months BNP No
   Feola et al. 2011 (38) 53 55 Epirubicin + cyclophosphamide + 5-fluorouracil Prospective 2 years BNP Yes
   Veronese et al. 2018 (44) 23 50 Doxorubicin + cyclophosphamide/paclitaxel Prospective 8 months BNP No
Data extracted from studies evaluating the cardiac marker CK-MB
   Silva et al. 2024 (52) 40 56 Doxorubicin Prospective 12 months CK-MB No
   De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months CK-MB Yes
40 Anthracyclines + taxanes + tratuzumab 12 months CK-MB Yes
   Şendur et al. 2015 (40) 164 49 Trastuzumab Prospective 9/52 weeks CK-MB No
   Yang et al. 2012 (46) 4 41 Epirubicin Clinical Trial 4 months CK-MB Yes
9 4 months CK-MB No
Data extracted from studies evaluating the cardiac marker myoglobin
   De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months Myoglobin Yes
40 Anthracyclines + taxanes + trastuzumab Prospective 12 months Myoglobin Yes
   Yang et al. 2012 (46) 4 41 Epirubicin Clinical Trial 4 months Myoglobin Yes
9 4 months Myoglobin No
Data extracted from studies evaluating the marker NT-proBNP
   Malik et al. 2016 (21) 33 49.4 5-fluorouracil + epirubicin + cyclophosphamide or 5-fluorouracil + epirubicin + cyclophosphamide or doxorubicin/paclitaxel or docetaxel Prospective 6 months NT-proBNP Yes
   Advani et al. 2017 (22) 11 51 Doxorubicin Prospective 2 cycles NT-proBNP Yes
11 60 Trastuzumab 2 cycles NT-proBNP Yes
   Kittiwarawut et al. 2013 (23) 52 50 Doxorubicin + cyclophosphamide Prospective 9 weeks NT-proBNP Yes
   Yu et al. 2016 (24) 69 53 Paclitaxel + trastuzumab + pertuzumab Prospective 3–38 months NT-proBNP No
   Tanindi et al. 2011 (25) 37 42 Doxorubicin + cyclophosphamide or doxorubicin + cyclophosphamide + 5-fluorouracil Prospective 45 days NT-proBNP Yes
   Demissei et al. 2019 (26) 159 49.2 Doxorubicin + cyclophosphamide + paclitaxel Prospective Up to 3.5 years NT-proBNP Yes
126 49.6 Trastuzumab + docetaxel or cyclophosphamide or carboplatin NT-proBNP Yes
29 52.1 Doxorubicin + cyclophosphamide/paclitaxel + trastuzumab NT-proBNP No
   von Hagens et al. 2019 (28) 13 57 Artesunate Clinical Trial 41 months NT-proBNP No
   Zardavas et al. 2017 (29) 452 Trastuzumab Prospective 1–2 years NT-proBNP Yes
   Matos et al. 2016 (30) 92 53.6 Trastuzumab Prospective 12 months NT-proBNP No
   De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months NT-proBNP Yes
40 Anthracyclines + taxanes + tratuzumab 12 months NT-proBNP Yes
   Silva et al. 2015 (18) 16 49 Doxorubicin + cyclophosphamide + tamoxifen or doxorubicin+ cyclophosphamide + 5-fluorouracil + tamoxifen or paclitaxel + tamoxifen Prospective 12 months NT-proBNP Yes
21 47 12 months NT-proBNP Yes
23 48 6 months NT-proBNP Yes
   Sawaya et al. 2011 (35) 43 47 Anthracyclines + trastuzumab Prospective 6 months NT-proBNP No
   Sawaya et al. 2012 (34) 81 50 Doxorubicin or epirubicin/paclitaxel + trastuzumab/trastuzumab Prospective 15 months NT-proBNP No
   Putt et al. 2015 (37) 78 49 Doxorubicin or paclitaxel + trastuzumab/trastuzumab Prospective Up to 15 months NT-proBNP No
   Şendur et al. 2015 (40) 164 49 Trastuzumab Prospective 1 year NT-proBNP No
   Ponde et al. 2018 (42) 172 50 Lapatinib or trastuzumab or lapatinib + trastuzumab Clinical Trials 2 weeks NT-proBNP No
173 18 weeks NT-proBNP No
   Fallah-Rad et al. 2011 (41) 42 47 Trastuzumab Prospective 1 year NT-proBNP No
   Frères et al. 2018 (45) 45 49 Cyclophosphamide + epirubicin/paclitaxel ± trastuzumab or lapatinib Prospective 3 months NT-proBNP Yes
   Goel et al. 2012 (47) 36 52 Trastuzumab Prospective 3 weeks NT-proBNP Yes
   Romano et al. 2012 (48) 71 54 Doxorubicin+ docetaxel or epirubicin + cyclephosphamide+5-fluorouracil Prospective 6 cycles NT-proBNP Yes
   Dhir et al. 2019 (49) 41 51.7 Trastuzumab Prospective 12 months NT-proBNP Yes
   van Boxtel et al. 2015 (50) 55 52.8 Docetaxel + doxorubicin + cyclophosphamide Prospective 1 year NT-proBNP Yes
   Ürün et al.2015 (51) – 48.5 Trastuzumab Prospective 52 weeks NT-proBNP Yes
Data extracted from studies evaluating the cardiac marker troponin I
   Yu et al. 2016 (24) 69 53 Paclitaxel + trastuzumab + pertuzumab Prospective 3–38 months Troponin I No
   Drafts et al. 2013 (27) 53 50 Doxorubicin Prospective 6 months Troponin I Yes
   Zardavas et al. 2017 (29) 452 50 Trastuzumab Prospective 1–2 years Troponin I Yes
   De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months Troponin I Yes
40 Anthracyclines + taxanes + tratuzumab 12 months Troponin I Yes
   Feola et al. 2011 (38) 53 55 Epirubicin + cyclophosphamide + 5-fluorouracil Prospective 2 years Troponin I Yes
   Şendur et al. 2015 (40) 164 49 Trastuzumab Prospective 9/52 weeks Troponin I No
   Morris et al. 2011 (43) 95 46 Doxorubicin + cyclophosphamide/paclitaxel + tras tuzumab + lapatinib/trastuzumab + lapatinib Prospective 18 months Troponin I Yes
   Veronese et al. 2018 (44) 23 50 Doxorubicin + docetaxel or epirubicin + cyclophosphamide + 5-fluorouracil Prospective 6 cycles Troponin I Yes
   van Boxtel et al. 2015 (50) 55 52.8 Docetaxel + doxorubicin + cyclophosphamide Prospective 1 year Troponin I Yes
Data extracted from studies evaluating the cardiac marker ultrasensitive troponin I
   Sawaya et al. 2011 (35) 43 47 Anthracyclines + trastuzumab Prospective 6 months Ultrasensitive troponin I Yes
   Sawaya et al. 2012 (34) 81 50 Doxorubicin or epirubicin/paclitaxel + trastuzumab/trastuzumab Prospective 15 months Ultrasensitive troponin I Yes
   Putt et al. 2015 (37) 78 49 Doxorubicin or paclitaxel + trastuzumab/trastuzumab Prospective Up to 15 months Ultrasensitive troponin I Yes
   Inanc et al. 2016 (39) 58 51 Doxorubicin + cyclophosphamide or docetaxel + doxorubicin + cyclophosphamide or 5-fluorouracil + epirubicin or 5-fluorouracil + epirubicin + cyclophosphamide prospective 21 days troponin I Prospective 21 days Ultrasensitive troponin I Yes
   Dhir et al. 2019 (49) 41 51.7 Trastuzumab Prospective 12 months Ultrasensitive troponin I No
Data extracted from studies evaluating cardiac marker the troponin T
   Abhidha Malik et al. 2016 (21) 33 49.4 5-fluorouracil + epirubicin + cyclophosphamide or 5-fluorouracil + epirubicin + cyclophosphamide or doxorubicin/paclitaxel or docetaxel Prospective 6 months Troponin T Yes
   Kittiwarawut et al. 2013 (23) 52 50 Doxorubicin + cyclophosphamide Prospective 9 weeks Troponin T No
   Zardavas et al. 2017 (29) 452 50 Trastuzumab Prospective 1–2 years Troponin T Yes
   De Iuliis et al. 2016 (31) 60 66 Anthracyclines + taxanes Prospective 12 months Troponin T Yes
40 Anthracyclines + taxanes + tratuzumab 12 months Troponin T Yes
   Ponde et al. 2018 (42) 172 50 Lapatinib or trastuzumab or lapatinib + trastuzumab Clinical Trial 2 weeks Troponin T No
173 18 weeks Troponin T No
   Fallah-Rad et al. 2011 (41) 42 47 Trastuzumab Prospective 1 year Troponin I No
   Frères et al. 2018 (45) 45 49 Cyclophosphamide + epirubicin/paclitaxel ± trastuzumab or lapatinib Prospective 3 months Troponin T Yes
   Yang et al. 2012 (46) 4 41 Epirubicin Clinical Trial 4 months Troponin Yes
9 4 months Troponin T No
   Goel et al. 2012 (47) 36 52 Trastuzumab Prospective 3 weeks Troponin T No
Data extracted from studies evaluating the cardiac marker high-sensitive troponin T
   Advani et al. 2017 (22) 11 51 Doxorubicin Prospective 2 cycles High-sensitive troponin T Yes
11 60 Trastuzumab 2 cycles High-sensitive troponin T No
   Demissei et al. 2019 (26) 159 49.2 Doxorubicin + cyclophosphamide/paclitaxel Prospective Up to 3.5 years High-sensitive troponin T Yes
126 49.6 Trastuzumab + docetaxel or cyclophosphamide or carboplatin High-sensitive troponin T Yes
29 52.1 Doxorubicin + cyclophosphamide/paclitaxel + trastuzumab High-sensitive troponin T Yes
   Kitayama et al. 2017 (36) 40 – Epirubicin + cyclophosphamide + 5-fluorouracil or trastuzumab or epirubicin + cyclophosphamide + 5-fluorouracil + tratuzumab Prospective Up to 18 months High-sensitive troponin T Yes
   Şendur et al. 2015 (40) 164 49 Trastuzumab Prospective 9/52 weeks High-sensitive troponin T No

BNP, brain natriuretic peptide; CK-MB, creatine kinase-MB fraction; NT-proBNP, N-terminal brain natriuretic peptide.

Discussion

Breast cancer remains one of the leading causes of mortality among women in Brazil and worldwide (1,2). Despite significant therapeutic advances, including the use of anthracyclines and anti-HER2 agents, these treatments are frequently associated with subclinical cardiotoxicity (21). As patient survival increases, the incidence of cardiac events has become a growing concern, potentially leading to treatment delays or interruptions and compromising oncologic outcomes.

A substantial difference was observed in the study designs reviewed, with 90% being prospective studies. This predominance may reflect the lower complexity of prospective designs compared to randomized, double-blind clinical trials. Among the biomarkers evaluated for cardiac dysfunction, NT-proBNP and troponins T (cTnT) and I (cTnI) were the most frequently used. Their widespread clinical application and higher sensitivity for detecting myocardial injury—even in non-oncologic populations—support their relevance in cardio-oncology. Notably, ultrasensitive troponin I (us-cTnI) was the best predictor of chemotherapy-induced cardiotoxicity, demonstrating predictive ability in 80% of the studies utilizing this method. NT-proBNP also emerged as a robust early predictor, detecting cardiotoxicity in 19 of the 29 studies reviewed. Nevertheless, due to study heterogeneity, definitive conclusions cannot be drawn.

The variability in study design, treatment regimens, duration, sample sizes, and methodologies for biomarker assessment hinder a uniform analysis of the data. However, NT-proBNP/BNP and troponins I and T consistently appeared as the most frequently assessed markers across studies (26,53). Michel et al. confirmed that both biomarkers serve as early predictors of cardiotoxicity in patients undergoing chemotherapy, and further discussed their role in cardioprotective strategies (12,53).

Supporting these findings, Curigliano and Cardinale et al. [2016] highlighted the importance of serial echocardiographic monitoring of left ventricular ejection fraction alongside measurement of troponins and natriuretic peptides (13). Follow-up studies reinforced this approach by demonstrating early biomarker elevation before clinical symptoms or structural abnormalities become apparent (10,12,51). Demissei et al. [2019] further contributed by identifying distinct cardiovascular risk profiles and promoting individualized monitoring (26). Additionally, novel inflammatory and remodeling biomarkers, such as ST2 and fibrinogen, are being investigated as complementary tools for assessing cardiotoxicity.

Beyond early detection, pharmacological strategies have also proven effective in prevention. Gao et al. [2023] demonstrated that ACE inhibitors and beta-blockers reduce the risk of cardiac dysfunction in breast cancer patients receiving chemotherapy. In this context, NT-proBNP proved to be a critical biomarker, with early elevation indicating cardiac stress even in asymptomatic individuals (54). The CHECK HEART-BC study by Terui et al. [2023] proposed a predictive model incorporating clinical and imaging data to stratify patients according to cardiotoxicity risk. These findings reinforce the value of an integrated, personalized approach that bridges oncology and cardiology (55).

Recently, Silva et al. [2025] introduced the concept of “permissive cardiotoxicity,” which advocates for the continuation of cancer treatment despite ventricular dysfunction, provided that strict monitoring and cardioprotective measures are implemented (56). This strategy acknowledges that immediate treatment discontinuation may significantly impact oncologic outcomes. Thus, individualized follow-up using imaging and biomarkers enables more balanced clinical decision-making. This approach aligns with current evidence on biomarker frequency and effectiveness in early cardiotoxicity detection, highlighting the importance of a collaborative and patient-centered care model in cardio-oncology.

Conclusions

Finally, it was found in the results that the high-sensitive (hs) troponin I and T cardiac markers, NT-proBNP demonstrated to be the sensitive biomarkers in detecting early cardiotoxicity under antineoplastic treatment. There is a need for research in search of new biomarkers that are capable of detecting asymptomatic cardiotoxicity and that early provide the opportunity to reverse side effects and improve the patient prognosis in the personalization of oncology patient conducts.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-24-136/rc

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-24-136/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-136/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: da Silva Soares TN, Gascón TM, Fonseca FLA, Murad N, de Carvalho SS, Veiga GLD, Alves BDCA, Pereira EC. Evaluation of cardiac markers in patients with breast cancer receiving antineoplastic treatment: a systematic review. Chin Clin Oncol 2025;14(6):76. doi: 10.21037/cco-24-136

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