Equivocal and definite interstitial lung abnormalities as risk factors for trastuzumab deruxtecan-related interstitial lung disease in breast cancer
Abstract
Background: Trastuzumab deruxtecan (T-DXd) is effective for advanced breast cancer but is associated with interstitial lung disease (ILD). The clinical relevance of baseline interstitial lung abnormalities (ILAs), including subtle equivocal findings, remains unclear.
Methods: This retrospective cohort study included consecutive patients with advanced or recurrent breast cancer who initiated T-DXd at a tertiary hospital in Japan between June 2020 and May 2025. Baseline CT before T-DXd initiation was reviewed for ILAs and classified as no ILA, equivocal ILA, or definite ILA. The cumulative incidence of T-DXd-related ILD was estimated using a competing-risk approach.
Results: Among 156 patients, baseline ILAs were identified in 50 patients: 21 with equivocal ILA and 29 with definite ILA. T-DXd-related ILD occurred in 31 patients (20%), including 19 of 50 patients (38%) in the ILA group and 12 of 106 patients (11%) in the non-ILA group. Baseline ILA was associated with a higher cumulative incidence of T-DXd-related ILD (subdistribution hazard ratio, 3.56; 95% CI, 1.63-7.78; P = .001). No significant difference in T-DXd-related ILD risk was detected between the equivocal and definite ILA groups. This association remained consistent in the <1.5-mm CT subgroup. No significant differences in progression-free or overall survival were observed according to baseline ILA status. Among patients with baseline ILA, 33 of 50 had ILAs first detected during prior systemic anticancer therapy.
Conclusions: Baseline ILAs, including equivocal findings, were associated with an increased risk of T-DXd-related ILD. ILAs were frequently first detected during prior systemic anticancer therapy before T-DXd initiation.
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BibTeX
@article{nakamura2026equivocal,
title = {{Equivocal and definite interstitial lung abnormalities as risk factors for trastuzumab deruxtecan-related interstitial lung disease in breast cancer}},
author = {Tomoaki Nakamura and Naoki Murata and Yukiko Hibino and Clara So and Atsushi Kitamura and Yutaka Tomishima and Torahiko Jinta},
journal = {The Oncologist},
year = {2026},
month = oct,
doi = {10.1093/oncolo/oyag420},
url = {https://doi.org/10.1093/oncolo/oyag420},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Equivocal and definite interstitial lung abnormalities as risk factors for trastuzumab deruxtecan-related interstitial lung disease in breast cancer
AU - Tomoaki Nakamura
AU - Naoki Murata
AU - Yukiko Hibino
AU - Clara So
AU - Atsushi Kitamura
AU - Yutaka Tomishima
AU - Torahiko Jinta
PY - 2026
DA - 2026/10/19
JO - The Oncologist
DO - 10.1093/oncolo/oyag420
UR - https://doi.org/10.1093/oncolo/oyag420
AB - Background: Trastuzumab deruxtecan (T-DXd) is effective for advanced breast cancer but is associated with interstitial lung disease (ILD). The clinical relevance of baseline interstitial lung abnormalities (ILAs), including subtle equivocal findings, remains unclear. Methods: This retrospective cohort study included consecutive patients with advanced or recurrent breast cancer who initiated T-DXd at a tertiary hospital in Japan between June 2020 and May 2025. Baseline CT before T-DXd initiation was reviewed for ILAs and classified as no ILA, equivocal ILA, or definite ILA. The cumulative incidence of T-DXd-related ILD was estimated using a competing-risk approach. Results: Among 156 patients, baseline ILAs were identified in 50 patients: 21 with equivocal ILA and 29 with definite ILA. T-DXd-related ILD occurred in 31 patients (20%), including 19 of 50 patients (38%) in the ILA group and 12 of 106 patients (11%) in the non-ILA group. Baseline ILA was associated with a higher cumulative incidence of T-DXd-related ILD (subdistribution hazard ratio, 3.56; 95% CI, 1.63-7.78; P = .001). No significant difference in T-DXd-related ILD risk was detected between the equivocal and definite ILA groups. This association remained consistent in the <1.5-mm CT subgroup. No significant differences in progression-free or overall survival were observed according to baseline ILA status. Among patients with baseline ILA, 33 of 50 had ILAs first detected during prior systemic anticancer therapy. Conclusions: Baseline ILAs, including equivocal findings, were associated with an increased risk of T-DXd-related ILD. ILAs were frequently first detected during prior systemic anticancer therapy before T-DXd initiation.
SN - 1083-7159
SN - 1549-490X
ER -