Taxanes-induced cardiotoxicity in patients with breast cancer: diagnosis and prediction

Introduction: Taxanes are powerful drugs, which increase survival and lower the recurrence rate of cancer, but their use is limited by cardiotoxicity. Early diagnosis and understanding the mechanisms of cardiotoxicity are essential in order to detect the patients at risk for irreversible heart failure. Aims: To describe new parameters for early diagnosis of taxanes-induced cardiotoxicity; to investigate the mechanisms and to defi ne predictive models for cardiotoxicity. Methods: 40 women with HER2- breast cancer (age 43 ± 8 years), scheduled to be treated with taxanes-based chemotherapy, were prospectively evaluated at baseline, aft er the 1st cycle, immediately (cumulative dose of 540 ± 150 g/m2), and 1 year aft er the completion of treatment by 4D auto LV quantifi cation echo to assess LVEF, and systolic deformation: radial (RS), longitudinal (LS), circumferential (CS) and area strain (AS); arterial stiff ness from β index; oxidative stress from Carbonyl Concentration into the Plasma Proteins – CCPP, and genetic variation of genotypes rs28371759, rs2032582, and rs1056836. Results: After the treatment, 13 patients developed cardiotoxicity (EF 51 ± 2% vs 63 ± 3%, p < 0.05) (group I), while 26 patients did not (group II). After the 1st cycle of taxanes, there were reductions in LS, and AS (-19 ± 3% vs -22 ± 2, and 33 ± 6% vs 39 ± 3%, p < 0.05), but patients from group I had significantly lower deformation (SL-19 ± 2% vs -22 ± 2%, and AS 31 ± 5% vs 41 ± 2%, p < 0.01), and increased arterial stiffness related to augmentation of oxidative stress (β: 10.2 ± 3 vs 7.7 ± 3; and CCPP: 0.500 ± 0.100 vs 0.336 ± 0.104 nmol/mg, p < 0.01). Genotype rs1056836 was related to the decrease of LVEF after the treatment (r = 0.59, p = 0.02). A decrease of AS with 18% aft er the 1st cycle of taxanes was the most powerful predictor of cardiotoxicity. Conclusions: Cardiotoxicity induced by taxanes immediately after completion of treatment in patients with breast cancer can be diagnosed and predicted by 4D LV deformation. Although recovered after 1 year of treatment, early cardiac dysfunction might be related to increased oxidative stress and arterial stiff ness, associated with a specific genetic variation.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)