Clinical and genetic predictions of early-onset cardiac toxicity in adjuvant chemotherapy for breast cancer

Abstract

Aim: To identify clinical and genetic variants associated with early-onset cardiac toxicity with a low cumulative dose of chemotherapy drugs in breast cancer. Methods: A total of 388 recruited patients completed routine blood, liver and kidney function, D-dimer, troponin T, brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, ECG and echocardiography tests before and after adjuvant chemotherapy. 25 single-nucleotide polymorphisms (SNPs) were tested. Results: A total of 277 adjuvant chemotherapy-related cardiac toxicity events were recorded in 180 patients (46.4%). Anthracycline-containing chemotherapy (odds ratio: 1.848; 95% CI: 1.135–3.008; p = 0.014) and the SLC28A3 rs885004 GG genotype (odds ratio: 2.034; 95% CI: 1.189–3.479; p = 0.010) were found to be associated with overall cardiac toxicity. The final predictive risk model consisting of clinical risk factors and SNPs was better than SNP alone (p = 0.006) or clinical risk factor alone (p = 0.065). Conclusion: On the basis of clinical factors, a prediction model with genetic susceptibility factors can better predict early-onset cardiac toxicity.

Keywords::

• breast cancer
• early-onset cardiac toxicity
• predictive risk model
• risk factors
• single-nucleotide polymorphisms

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1021

Author contributions

Conception and design: B Liu, X Guan, H Li and F Ma. Data recording: B Liu and X Sun. Data analysis: B Liu and Z Yi. Manuscript drafting and reviewing: all authors.

Data sharing

The preprint of the manuscript was posted on 27 Mar 2020 in Research Square. (https://www.researchsquare.com/article/rs-18261/v1).

Financial & competing interests disclosure

The present study was supported by Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-014) and National Natural Science Foundation of China (No. 82172875). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funded writing was provided by the corresponding author F Ma at his own expense.

Ethical conduct of research

This study was approved by the Institutional Review Boards of Cancer Hospital, Chinese Academy of Medical Sciences (no. NCT03537339), and the protocol has been registered on ClinicalTrials.gov with the number NCC201712029. This study did not interfere with any decisions made by doctors and did not change or delay any treatments. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The present study was supported by Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-014) and National Natural Science Foundation of China (No. 82172875). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.