@article{8605c546e8884c879732e31ea9de1e00,
title = "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",
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",
author = "Chang, {Chen Han} and Jung, {Chiau Jing} and Huang, {Yi Ming} and Lo Chiao and Chang, {Yih Leong} and Hsieh, {Song Chou} and Lin, {Ching Hung} and Kuo, {Yu Min}",
note = "Funding Information: This work was supported by Ministry of Science and Technology (MOST 108-2314-B-002-097-MY3 , 107-2314-B-002-253 -, 106-2314-B-002-100 -), National Taiwan University Hospital ( NTUH 110-M4972 ) and Taiwan Rheumatology Association Research Fund ( TRARF-2018 ). Funding Information: This article was subsidized for English editing by National Taiwan University under the Excellence Improvement Program for Doctoral Students (grant number 108-2926-I-002-002-MY4 ), sponsored by the Ministry of Science and Technology, Taiwan . Funding Information: 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.This article was subsidized for English editing by National Taiwan University under the Excellence Improvement Program for Doctoral Students (grant number 108-2926-I-002-002-MY4), sponsored by the Ministry of Science and Technology, Taiwan.This work was supported by Ministry of Science and Technology (MOST 108-2314-B-002-097-MY3, 107-2314-B-002-253-, 106-2314-B-002-100-), National Taiwan University Hospital (NTUH 110-M4972) and Taiwan Rheumatology Association Research Fund (TRARF-2018). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = feb,
doi = "10.1016/j.breast.2021.11.016",
language = "English",
volume = "61",
pages = "35--42",
journal = "Breast",
issn = "0960-9776",
publisher = "Churchill Livingstone",
}
