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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

716 - Predicting the occurrence and prevention of early anthracycline cardiotoxicity of chemotherapy in patients with breast cancer

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Supportive Care and Symptom Management

Tumour Site

Breast Cancer

Presenters

Anton Askolskyi

Citation

Annals of Oncology (2018) 29 (suppl_8): viii603-viii640. 10.1093/annonc/mdy300

Authors

A. Askolskyi1, L. Syvak1, O. Zharinov2, N. Khranovska3

Author affiliations

  • 1 Chemotherapy Of Solid Tumors, National Cancer Institute, 03022 - Kiev/UA
  • 2 Department Of Functional Diagnostics, Shupyk National Medical Academy of Postgraduate Education, Ministry of Healthcare of Ukraine, Kiev/UA
  • 3 Laboratory Of Experimental Oncology And Laboratory Of Molecular-genetics Diagnostics, National Cancer Institute, 03022 - Kiev/UA
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Resources

Abstract 716

Background

Methylenetetrahydrofolate Reductase (MTHFR) is the key enzyme of xenobiotic detoxification, involved in the metabolism of anticancer drugs. Genotyping of the polymorphism MTHFR allows to make prognosis of chemotherapy side effects in different patients, personalize pharmacotherapy.

Methods

QTc interval and myocardial systolic and diastolic function of 100 patients with breast cancer stages T1-3N0-3M0 treated with neo/adjuvant anthracycline chemotherapy were investigated. In the main study group 50 patients received cardioprotective medications (enalapril 2.5 mg orally twice daily and carvedilol 6.25 mg orally twice daily). The polymorphisms of MTHFR gene in control group were evaluated using Real-Time PCR. Statistica10.0 software was used to perform analysis of variance.

Results

It was established that the specific manifestations of early cardiotoxicity of doxorubicin at a cumulative dose 300 mg/m2 were QTc prolongation over 460 msec in the main group in 5 (10%) patients, in the control group − 13 (26%) patients, as well as diastolic dysfunction (DD) of the left ventricle type 1 in the main group in 5 (10%) patients, in the control group − 15 (30%) patients.The absence of cardioprotective therapy in our study was a risk factor for these complications: QTc interval prolongation (OR = 3.15, 2.05 − 4.21, p = 0.03) and DD (OR = 3.85, 2.75 − 4.96, p = 0.01).A molecular genetic analysis had shown that QT prolongation and DD were detected in 36.4% of patients with T/T genotype, in 36.6% − with C/T genotype and only 9.1% patients with genotype C/C. The risk of cardiotoxicity of chemotherapy in patients with breast cancer, which is the carrier of one or two mutant alleles of the gene MTHFR (genotype C/T and T/T) is 2.68 times higher (OR = 2.68; 95% CI = 1.24 − 5.78; p < 0.01) in comparison with carriers of genotype C/C.

Conclusions

It is reasonable to determine the MTHFR gene polymorphism in patients with early breast cancer prior to treatment which allow to identifying a high-risk cardiotoxicity group for timely and adequate cardioprotective therapy administration.

Clinical trial identification

Legal entity responsible for the study

National Cancer Institute, Kiev, Ukraine.

Funding

National Cancer Institute, Kiev, Ukraine.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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