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Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up

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Abstract

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent’s University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m2 and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m2. Median Dox dose was 240 mg/m2 [225–298]; 92 patients (59.7 %) received ≤240 mg/m2 and 62 (40.3 %) > 240 mg/m2. Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9–36.5] and 21.1 pg/ml [9.8–37.7] in those without LVD and 61.5 pg/ml [50–68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

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Acknowledgements

We wish to thank the patients who participated in the study, as well as the support staff of the STOP-HF project and Oncology departments for their help in completing this study.

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Correspondence to J. M. Walshe.

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Conflict of interest

Gillian Murtagh has been an employee of Abbott Diagnostics since 7/6/15, but was not an employee at the time of the study. Abbott played no role in study design, conduct, or funding. John Crown has received Honoraria and a Speakers Bureau from Eisai and Genomic Health; Research Funding from Roche and GSK; and Travel, Accommodation and Expenses from BMS and Roche. All the remaining authors have disclosed no conflict of interest.

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G. Murtagh and T. Lyons have contributed equally to the manuscript.

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Murtagh, G., Lyons, T., O’Connell, E. et al. Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up. Breast Cancer Res Treat 156, 501–506 (2016). https://doi.org/10.1007/s10549-016-3781-4

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  • DOI: https://doi.org/10.1007/s10549-016-3781-4

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