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Data-driven Cancer Research Conference 2026
24-26 February 2026 | Edinburgh, Scotland
P30
Incidence and risk factors for cardiovascular toxicity of anthracycline-based chemotherapy regimens in non-metastatic breast cancer treatment: a systematic review and meta-analysis of interventional and observational research
Poster Presenter
Part of Topic
Incidence and risk factors for cardiovascular toxicity of anthracycline based chemotherapy regimens in non-metastatic breast cancer treatment: a systematic review of interventional and observational research.
Matthew Hazell1, Helena Carreira1, Krishnan Bhaskaran1, Alexander Lyon2, Julian Matthewman1, Shamsudeen Mohammed1, Alistair Ring3, Anoop Shah1, William Wilson1 and Harriet Forbes1
1 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London. 2 Royal Brompton Hospital, London. 3 The Royal Marsden, London. ✉ matthew.hazell1@lshtm.ac.uk
Background:
•Anthracycline use in early and locally advanced breast cancer is limited by concerns over cardiovascular toxicity (CVT), particularly the long-term risk of heart failure and cardiomyopathy (HF/CM).
•Changes to clinical practice over the last two decades have likely reduced the risk to patients of anthracycline-induced CVT.
•Contemporary evidence on the absolute and relative risk of anthracycline-induced CVT in breast cancer survivors, and how it varies across patient subgroups, remains unclear.
Aim:
•To synthesise current evidence on the risk of HF/CM in early and locally advanced breast cancer patients treated with anthracycline-containing regimens compared with alternative or no systemic anticancer therapy.
•Secondary objectives:
-Evaluate the risk of CVD death from anthracyclines.
-Evaluate which patient subgroups are at an increased risk of anthracycline-induced CVT.
Methods:
Study design: Systematic review.
Search: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to April 2025.
Eligibility: RCTs, cohort, and case-control studies if they reported HF/CM with at least one year of follow up for women with early and locally advanced breast cancer who did and did not receive anthracycline-containing regimen, with a sample size of ≥100.
Screening and extraction: Screened by one reviewer, a second reviewer independently screened a random sample of 500 titles and abstracts and 116 (10%) full text articles to assess validity.
Study quality: Detailed study-specific criteria produced for each study design.
Data synthesis: Results were summarised graphically and narratively.
Results:
•Majority of studies conducted in Europe or North America. Most observational studies used population-based medical records.
•5 RCTs and 1 observational study were rated as low risk of bias.
•Among anthracycline exposed, the absolute proportion who developed HF/CM ranged from 0% to 5.2% in RCTs. In observational studies, cumulative incidence over five to ten years of follow up ranged from 3.1% to 30.1%.
•An RCT (Albain et al, 2009) compared anthracyclines to no chemotherapy reporting HF/CM in both arms, finding an 11 times increased risk for those that received anthracyclines (Figure 2a). Among 9 observational comparisons (5 studies), 8 reported an increased risk of HF/CM from anthracyclines ranging from 12% to 619%, compared to no chemotherapy (Figure 2b).
•Compared to non-anthracycline chemotherapy, of the four RCTs (five comparisons) that reported HF/CM in both arms, anthracyclines were associated with increased risks of HF/CM; effect estimates ranged from 2.21 to 10.57 (Figure 2a). Two cohorts reported a 50% to 100% increased risk of HF/CM from anthracyclines, whilst Morais Mata et al, 2024 reported a reduced risk, compared to non-anthracycline chemotherapy (Figure 2b).
•Compared to non-anthracycline chemotherapy with trastuzumab, anthracyclines and trastuzumab were associated with a substantially increased risk in the largest RCT, two RCTs reported few results limiting precision (Figure 2a). Cohort studies reported mixed results (Figure 2b).
•Of the three RCTs that reported on CVD death, only one cardiac death occurred, in a non-anthracycline arm.
•Bowles et al, 2012 reported a treatment interaction with age, with the biggest increase in HF/CM from anthracyclines compared to no chemotherapy seen in younger women. Two studies reported increasing HF/CM with anthracycline dose, but Banke et al, 2018 reported no difference. Trastuzumab with anthracyclines was associated with an increased HF/CM risk in three studies.
Conclusions:
•The included studies broadly suggested a range of increased risks of HF/CM from anthracycline chemotherapy compared to no chemotherapy and non-anthracycline chemotherapies, with limited data for comparisons to trastuzumab alone and non-anthracycline chemotherapies and trastuzumab.
•There is a lack of consistency in trial and real-world risks of HF/CM among people receiving anthracyclines. The magnitude of the reported increased risk of HF/CM from anthracyclines was greater in RCTs than observational studies, suggesting bias due to confounding by indication in observational studies.
•There is very limited data on anthracycline associated CVD death.
•No evidence on which patient sub-groups, such as ethnicity, comorbidities, deprivation and cancer subtype, were at an increased risk of anthracycline-induced HF/CM.
MH is supported by a Medical Research Council Intercollegiate Doctoral Training Partnership Studentship (Grant no MR/W006677/1). The funders had no role in developing this study.