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. 2021 Apr;186(3):851-862.
doi: 10.1007/s10549-020-06039-w. Epub 2021 Jan 4.

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

N I Bouwer  1   2 , T G Steenbruggen  3 , J van Rosmalen  4 , H N Rier  5 , J J E M Kitzen  6 , M L van Bekkum  7 , A J Ten Tije  8 , P C de Jong  9 , J C Drooger  10 , C Holterhues  11 , C H Smorenburg  3 , M J M Kofflard  12 , E Boersma  13 , G S Sonke  3 , M-D Levin  6 , A Jager  5
Affiliations

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

N I Bouwer et al. Breast Cancer Res Treat. 2021 Apr.

Abstract

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted.

Methods: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40-50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab.

Results: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8-31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity.

Conclusions: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.

Keywords: Cardiotoxicity; HER2-positive metastatic breast cancer; LVEF monitoring; Screening for cardiotoxicity; Trastuzumab treatment.

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Conflict of interest statement

TGS received funding from Memidis Pharma outside the current project. GSS has received institutional research funding from AstraZeneca, Merck, Novartis and Roche. The other authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Yearly incidence of non-severe + severe cardiotoxicity and severe cardiotoxicity during long-term trastuzumab treatment
Fig. 2
Fig. 2
Cumulative incidence of non-severe + severe and severe cardiotoxicity with respect to the number of relevant risk factors. Note Solid lines indicate cumulative incidence; dashed lines indicate corresponding 95% CI of the cumulative incidence. For non-severe + severe cardiotoxicity, the following risk factors were included: BMI > 30 kg/m2, smoking and cardiotoxicity during prior neoadjuvant/ adjuvant treatment with trastuzumab and/or anthracyclines (Table 2). For severe cardiotoxicity, the following risk factors were included: smoking, cardiotoxicity during prior neoadjuvant/adjuvant treatment with trastuzumab and/or anthracyclines and baseline LVEF < 60% (Table 3)
Fig. 3
Fig. 3
Swimmers plot of all patients who developed cardiotoxicity and received LVEF measurements thereafter (n = 74).
See this image and copyright information in PMC

References

    1. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–1672. doi: 10.1056/NEJMoa052306. - DOI - PubMed
    1. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–1684. doi: 10.1056/NEJMoa052122. - DOI - PubMed
    1. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–792. doi: 10.1056/NEJM200103153441101. - DOI - PubMed
    1. Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, Herrmann J, Porter C, Lyon AR, Lancellotti P, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–190. doi: 10.1016/j.annonc.2019.10.023. - DOI - PMC - PubMed
    1. Petrelli F, Barni S. A pooled analysis of 2618 patients treated with trastuzumab beyond progression for advanced breast cancer. Clin Breast Cancer. 2013;13(2):81–87. doi: 10.1016/j.clbc.2012.11.008. - DOI - PubMed