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Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)

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Abstract

Background

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.

Methods

This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.

Results

173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.

Conclusion

These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

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Acknowledgements

Dr. Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium).

Funding

This research has received research grant from “Les Amis de L’Institut Bordet” (Grant 2016-02).

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Correspondence to Evandro de Azambuja.

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Conflicts of interest

The authors of this manuscript hereby declare the following conflicts of interest regarding this manuscript: Dimitrios Zardavas—Research Grants to his institution from Roche, Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Puma Biotechnology; Jens Huober—Roche honoraria and advisory role, Novartis: honoraria and advisory role, GSK: research funding; Evandro de Azambuja—received honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work; Martine Piccart—is a board member of Radius, is a consultant (honoraria): AstraZeneca, Lilly, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Crescendo Biologics, Periphagen, Huya, Debiopharm, PharmaMar and has received research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche-Genentech, Synthon, Radius, Servier. All remaining authors have declared no conflicts of interest.

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Ponde, N., Bradbury, I., Lambertini, M. et al. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Res Treat 168, 631–638 (2018). https://doi.org/10.1007/s10549-017-4628-3

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