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Case Reports
. 2022 Feb:61:35-42.
doi: 10.1016/j.breast.2021.11.016. Epub 2021 Nov 29.

The first reported case of trastuzumab induced interstitial lung disease associated with anti-neutrophil cytoplasmic antibody vasculitis - A case report and a prospective cohort study on the usefulness of neutrophil derived biomarkers in monitoring vasculitis disease activity during follow-up

Chen-Han Chang  1 , Chiau-Jing Jung  2 , Yi-Ming Huang  3 , Lo Chiao  4 , Yih-Leong Chang  5 , Song-Chou Hsieh  6 , Ching-Hung Lin  7 , Yu-Min Kuo  8
Affiliations
Case Reports

The first reported case of trastuzumab induced interstitial lung disease associated with anti-neutrophil cytoplasmic antibody vasculitis - A case report and a prospective cohort study on the usefulness of neutrophil derived biomarkers in monitoring vasculitis disease activity during follow-up

Chen-Han Chang et al. Breast. 2022 Feb.

Abstract

Targeted therapies against human epidermal growth factor receptor 2 (HER2) are associated with increased interstitial lung disease (ILD). Trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine have markedly extended HER2 breast cancer survival but current knowledge on how these HER2-targeted agents induce interstitial lung disease is still poorly defined due to limited cases in the literature. Physicians mostly managed this complication by dose interruption, dose de-escalation, or discontinuation with success. In 2019, the FDA had granted accelerated approval on trastuzumab deruxtecan (T-Dxd) in HER2 breast cancer in the late line setting. Severe ILD incidence rate was over ten percent and led to fatal outcomes in 2.2% of patients in the T-Dxd trial. Searching for biomarkers to detect ILD incidence before it becomes clinically fulminant or for treatment response monitoring is of high clinical value. A Case of life-threatening trastuzumab-induced ILD was encountered in our facility. The ILD was confirmed to be antineutrophil cytoplasmic antibody (ANCA) pulmonary capillaritis. The biomarker of neutrophil extracellular traps (NETs), serum MPO-DNA complex, showed a good correlation with the clinical severity. Soon after B cell depleting agent rituximab usage, the serum MPO-DNA outperformed ANCA autoantibody and maintained its correlation with clinical severity. In addition to the trastuzumab-induced ILD case, a prospective cohort in our facility also confirmed the usefulness of MPO-DNA in monitoring vasculitis activity. We postulated that upfront testing with biomarkers of vasculitis during HER2 targeted treatment with high ILD incidence may be beneficial in the future.

Keywords: Antineutrophil cytoplasmic antibody; Breast cancer; Interstitial lung disease; Trastuzumab.

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Conflict of interest statement

Declaration of competing interest The author(s) had declared that no conflicts of interest exist.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
A-D. (A) Chest radiograph (CXR) at initial presentation revealed multi-lobar consolidation with a centi-hilar pattern. (B) CXR on the third day showed rapid bilateral pulmonary infiltrate progression (C–D) Computed tomography (CT) on the third day showed a diffuse, multi-lobar consolidation with a peri-bronchovascular pattern.
Fig. 2
Fig. 2
A-B Bronchoscopy examination of the tracheal (A) and main carina (B) revealed fresh blood in the whole airway without active vascular bleeding.
Fig. 3
Fig. 3
A Lung, left upper lobe, wedge resection, low power field (100X), interstitial fibrosis with collagen deposits (C) and alveolar airspace obliteration (A). B High power field showing alveolar hemorrhage (A), and necrotic neutrophils (P) in a capillary wall (V) and alveoli. C Comparison of the patient sample to a sample from a healthy individual shows marked airspace obliteration due to hemorrhage and interstitial thickening.
See this image and copyright information in PMC

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