Enhertu-Induced Cryptogenic Organizing Pneumonia: Case Report and Review

Enhertu-Induced Cryptogenic Organizing Pneumonia: Case Report and Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Enhertu-Induced Cryptogenic Organizing Pneumonia: Case Report and Review Lisanwork Mikiyas Kebede, Yidnekachew Demssis Awoke, Hanna Genene Ruga, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7868590/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Bulletin of the National Research Centre → Version 1 posted 9 You are reading this latest preprint version Abstract Trastuzumab deruxtecan (T-DxD, Enhertu) is a HER2-directed antibody–drug conjugate that has expanded treatment options for patients with HER2-positive and HER2-low breast cancer. However, its use is associated with interstitial lung disease (ILD), most commonly manifesting as cryptogenic organizing pneumonia (COP), which can be life-threatening. We present the case of a 41-year-old woman with a history of invasive ductal carcinoma of the breast who developed acute dyspnea one week after her first dose of Enhertu. High-resolution chest computed tomography revealed radiographic features consistent with organizing pneumonia, along with metastatic disease and left hemidiaphragm paralysis. This case highlights the critical importance of early recognition and management of Enhertu-induced ILD. A review of the literature underscores the need for vigilant surveillance, timely imaging, and prompt initiation of corticosteroid therapy to mitigate morbidity and mortality. Enhertu represents a major therapeutic advance, but its pulmonary toxicity necessitates a structured, multidisciplinary approach to patient monitoring and care. Figures Figure 1 Case Presentation A 41-year-old woman presented with a left breast lump, initially reported on FNAC as possible fibroadenoma. Core biopsy revealed a 3 cm invasive ductal carcinoma, ER-positive, PR- and HER2-Low Positive. She underwent left mastectomy 2 years Back with pathology showing no residual tumor and 1/11 lymph nodes positive with lymphovascular and perineural invasion. CT chest and abdomen were normal back then. She has no family history of breast cancer and completed adjuvant chemotherapy with 4 cycles of AC (Adriamycin + Cyclophosphamide) followed by 4 cycles of paclitaxel in March 2024, becoming amenorrheic after the second cycle. On examination, there was no supraclavicular or axillary lymphadenopathy, and the mastectomy scar had a seroma. CBC was normal with marginally elevated counts, and vitamin D was low. She was started on tamoxifen and vitamin D supplementation. Currently She Presented with Shortness of breath of 3 Days duration after she took one dose of ENHERTU one week back. At presentation BP was 108/70 she was tachycardic to the level of 121 T- 36.0 and SPO2- 88% on Room air. On Physical Examination She had Bilateral Coarse crackles on the lower 1/3 of Bilateral Lungs. Laboratory Revealed WBC 1.6K with Neutrophil of 65% and Hemoglobin 12.2 Platelet 121K CRP 19.9. High Resolution Chest CT Scan on Fig. 1 Showed changes of Chronic Organizing Pneumonia, Bone and Left Supraclavicular area Metastasis and Left Hemidiaphragm Paralysis. She improved with intravenous Steroid and Broad spectrum Antibiotics for 4 Days and The Symptoms Improved. The Steroid Gradually Tapered and Discharged with PO antibiotics. Discussion Trastuzumab deruxtecan (T-DxD, Enhertu) is a HER2-directed antibody–drug conjugate comprising a humanized anti-HER2 monoclonal antibody linked via a cleavable peptide linker to a potent topoisomerase I inhibitor payload (DXd), featuring an average drug-to-antibody ratio of eight. Following HER2 binding, the conjugate is internalized, and in lysosomes the linker is cleaved, releasing DXd, which induces DNA damage and apoptosis in tumor cells [ 1 ]. This targeted cytotoxic design underpins its therapeutic potency but also contributes to its distinct adverse event profile. Initially approved for unresectable or metastatic HER2-positive breast cancer post prior anti-HER2 therapy, Enhertu’s indications have expanded to include HER2-low and HER2-ultralow breast cancers, both hormone receptor–positive and negative, in patients exposed to endocrine or chemotherapy regimens [ 2 , 3 ]. These broadening indications reflect its efficacy across varying levels of HER2 expression, expanding its clinical applicability [ 4 ]. Interstitial lung disease (ILD), including cryptogenic organizing pneumonia (COP), is a notable and potentially fatal adverse effect of Enhertu. This risk emerged in early clinical trials and has since been validated in pooled safety data. ILD affects approximately 12% of treated patients (at the 5.4 mg/kg dose), typically presenting around a median of 5.5 months into therapy, with fatal outcomes in approximately 0.9% of cases [ 2 , 5 ]. Pooled analyses further identified risk factors such as older age, baseline lung disease, and Japanese ethnicity [ 6 ]. The underlying pathophysiology of T-DxD–associated ILD remains incompletely elucidated. Leading hypotheses involve direct pulmonary toxicity from off-target DXd deposition, immune-mediated inflammatory injury, and bystander effects due to the payload’s membrane permeability and high drug-to-antibody ratio [ 7 , 8 ]. Broader reviews of drug-induced ILD emphasize immune dysregulation, oxidative stress, and alveolar epithelial injury as convergent mechanisms [ 9 ]. Imaging, notably high-resolution computed tomography (HRCT), is crucial for timely diagnosis and monitoring of Enhertu-related ILD. HRCT excels in detecting ground-glass opacities, consolidations, and perilobular patterns indicative of COP. In multicenter studies, COP was the most common radiographic pattern (72%), with mixed OP/hypersensitivity pneumonitis (HP), acute interstitial pneumonia/ARDS, and pure HP also reported [ 10 , 11 ]. A recent multicenter analysis further detailed correlations between imaging phenotypes and clinical outcomes, underscoring HRCT’s role in guiding both diagnosis and prognosis [ 12 ]. Clinical manifestations of Enhertu-associated ILD span a spectrum from asymptomatic, incidentally detected grade 1 findings to life-threatening grade 5 pneumonitis. Grade 1 ILD is managed by interrupting therapy until resolution (with or without corticosteroids), potentially allowing rechallenge at the same or reduced dose. In contrast, grade 2 or higher mandates permanent discontinuation and immediate initiation of systemic corticosteroids (e.g., prednisolone ≥ 1 mg/kg/day) with gradual tapering over at least four weeks [ 2 , 13 ]. Expert consensus now emphasizes baseline pulmonary evaluation, proactive HRCT surveillance, and early corticosteroid initiation as best practices [ 14 ]. Select case series demonstrate successful rechallenge after full recovery under rigorous clinical and imaging monitoring [ 15 ]. In summary, trastuzumab deruxtecan constitutes a significant therapeutic advance in HER2-targeted oncology, effectively extending options across the HER2 expression continuum [ 2 – 4 ]. However, its association with ILD—most commonly manifesting with COP patterns—necessitates vigilant surveillance, patient education, and structured management protocols. Early detection via HRCT, prompt intervention, and individualized decision-making are essential to maximize clinical benefit while minimizing morbidity and mortality. protocols. Early detection via HRCT, prompt intervention, and individualized decision-making are essential to maximize clinical benefit while minimizing morbidity and mortality. Declarations Ethics approval and consent to participate The family of the patient has provided written informed consent for the publication of their case details and any related images. Approval for this case report was not required to secure from the Ethics Committee of the institution. Consent for publication Written informed consent was obtained from the family of the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Availability of data and materials The data supporting the findings of this case report are included within the article. Additional information is available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No funding was received. Acknowledgment Not Applicable Code Availability Not applicable. No software code was used in this work. Authors’ contribution Lisanwork Mikiyas Kebede: Writing– original draft of the manuscript, review & editing, Coneceptualization, Visualization. Yidnekachew Demssis Awoke: Writing– review & editing, Data curation, Resources. Hana Genene Ruga: Writing– review & editing, Data curation. Feruza Mahmud Mehammed : Writing– review & editing, Data curation. Edelawit Tasena Noza: Writing– review & editing, Data curation. Author’s Information Name Email Institution Lisanwork Mikiyas Kebede [email protected] Lancet General Hospital Yidnekachew Demssis Awoke [email protected] Lancet General Hospital Hana Genene Ruga [email protected] Lancet General Hospital Feruza Mahmud Mehammed [email protected] Lancet General Hospital Edelawit Tasena Noza [email protected] Lancet General Hospital References European Medicines Agency. Enhertu – Product Information [Internet]. 2025 [cited 2025 Aug 11].Availablefrom: https://www.ema.europa.eu/en/documents/product-information/enhertu-epar-product-information_en.pdf U.S. Food and Drug Administration. Enhertu (trastuzumab deruxtecan) Label [Internet]. 2025 [cited2025Aug11].Availablefrom: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761139s032s035lbl.pdf Modi S, Saura C, Yamashita T, Park YH, Kim S-B, Tamura K, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. Cortes J, Cescon DW, Rugo HS, Im S-A, Wanders J, Friedrich R-J, et al. Trastuzumab deruxtecan for breast cancer with HER2-low expression: pooled analysis of safety and efficacy. Lancet Oncol. 2023;24(4):451–63. Enhertu HCP Site. Managing ILD/Pneumonitis [Internet]. 2025 [cited 2025 Aug 11]. Available from: https://www.enhertuhcp.com/en/managing-adverse-reactions/interstitial-lung-disease-pneumonitis Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, et al. Risk factors for interstitial lung disease induced by trastuzumab deruxtecan: pooled analysis from clinical trials. Cancer Sci. 2022;113(7):2214–24. Kubo T, Calvo A, King T, Matsumoto K, Ando M, Padera RF, et al. Safety review: mechanisms of drug-induced interstitial lung disease with antibody-drug conjugates. Breast Cancer Res Treat. 2022;189(3):605–15. ASCO Oncology. Commentary: pulmonary toxicity of antibody–drug conjugates. J Oncol Pract. 2023;19(2):85–9. Camus P, Kudoh S, Ebina M. Drug-induced interstitial lung disease: mechanisms and best practices for management. Eur Respir J. 2022;59(2):2102446. Tsuchiya Y, Marumo H, Takahashi H, Watanabe T, Ito S, Suzuki K, et al. CT imaging patterns of trastuzumab deruxtecan–related pneumonitis: OP vs HP phenotypes. Radiol Case Rep. 2023;18(4):1021–9. Enomoto Y, Yamazaki K, Ikeda S, Fujimoto K, Ogura T, Tazawa R, et al. Post-marketing surveillance: clinical and imaging features of trastuzumab deruxtecan–related ILD in Japan. Int J Clin Oncol. 2023;28(11):2125–35. Nagai H, Muro K, Horiike A, Matsumoto T, Nishino M, Kato T, et al. Imaging characteristics and clinical outcomes of trastuzumab deruxtecan–related pneumonitis: a multicenter study. Eur J Cancer. 2023;184:1–10. Medscape. Enhertu (trastuzumab deruxtecan) dosing and ILD guidelines [Internet]. 2025 [cited 2025 Aug 11]. Available from: https://reference.medscape.com/drug/enhertu-trastuzumab-deruxtecan-4000032 Jerusalem G, Park YH, Yamashita T, Kim S-B, Tamura K, Hamilton E, et al. Management of trastuzumab deruxtecan–associated interstitial lung disease: expert consensus and guidelines. ESMO Open. 2023;8(3):100782. Nakagawa K, Tsurutani J, Takahashi S, Yamaguchi K, Toyama T, Iwata H, et al. Rechallenge with trastuzumab deruxtecan after resolution of drug-induced ILD: outcomes from case series. J Thorac Oncol. 2024;19(2):195–203. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Bulletin of the National Research Centre → Version 1 posted Editorial decision: Revision requested 29 Dec, 2025 Reviews received at journal 26 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviews received at journal 12 Dec, 2025 Reviewers agreed at journal 11 Dec, 2025 Reviewers invited by journal 21 Oct, 2025 Editor assigned by journal 16 Oct, 2025 Submission checks completed at journal 16 Oct, 2025 First submitted to journal 15 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7868590","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":538187598,"identity":"d6e57800-2cde-44da-be2f-212af9a3d0b1","order_by":0,"name":"Lisanwork Mikiyas 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1","display":"","copyAsset":false,"role":"figure","size":878696,"visible":true,"origin":"","legend":"\u003cp\u003eStatus Post Left Breast Mastectomy, Left Axillary Area Fluid Collection Likely Post surgery Changes With Seroma, Left Supraclavicular area Large Mass- Likely Bone and Left Supraclavicular Area Metastasis, Bilateral Lungs Subpleural \u0026amp; Peribronchovascular patchy consolidation and Ground Glass Opacity with areas of ATOL sign more on the right side- Chronic Organizing Pneumonia, Significant elevation of the Left Hemidiaphragm :- Laryngeal Eventration\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7868590/v1/4728254a7806f7bec3beeb36.jpeg"},{"id":103766344,"identity":"cd196446-7fee-4b60-9207-d820f7257928","added_by":"auto","created_at":"2026-03-02 16:14:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1232539,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7868590/v1/4d95db61-07d6-452b-b6c6-583b739492a4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Enhertu-Induced Cryptogenic Organizing Pneumonia: Case Report and Review","fulltext":[{"header":"Case Presentation","content":"\u003cp\u003eA 41-year-old woman presented with a left breast lump, initially reported on FNAC as possible fibroadenoma. Core biopsy revealed a 3 cm invasive ductal carcinoma, ER-positive, PR- and HER2-Low Positive. She underwent left mastectomy 2 years Back with pathology showing no residual tumor and 1/11 lymph nodes positive with lymphovascular and perineural invasion. CT chest and abdomen were normal back then. She has no family history of breast cancer and completed adjuvant chemotherapy with 4 cycles of AC (Adriamycin\u0026thinsp;+\u0026thinsp;Cyclophosphamide) followed by 4 cycles of paclitaxel in March 2024, becoming amenorrheic after the second cycle. On examination, there was no supraclavicular or axillary lymphadenopathy, and the mastectomy scar had a seroma. CBC was normal with marginally elevated counts, and vitamin D was low. She was started on tamoxifen and vitamin D supplementation.\u003c/p\u003e\u003cp\u003eCurrently She Presented with Shortness of breath of 3 Days duration after she took one dose of ENHERTU one week back. At presentation BP was 108/70 she was tachycardic to the level of 121 T- 36.0 and SPO2- 88% on Room air. On Physical Examination She had Bilateral Coarse crackles on the lower 1/3 of Bilateral Lungs. Laboratory Revealed WBC 1.6K with Neutrophil of 65% and Hemoglobin 12.2 Platelet 121K CRP 19.9. High Resolution Chest CT Scan on Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e Showed changes of Chronic Organizing Pneumonia, Bone and Left Supraclavicular area Metastasis and Left Hemidiaphragm Paralysis. She improved with intravenous Steroid and Broad spectrum Antibiotics for 4 Days and The Symptoms Improved. The Steroid Gradually Tapered and Discharged with PO antibiotics.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTrastuzumab deruxtecan (T-DxD, Enhertu) is a HER2-directed antibody\u0026ndash;drug conjugate comprising a humanized anti-HER2 monoclonal antibody linked via a cleavable peptide linker to a potent topoisomerase I inhibitor payload (DXd), featuring an average drug-to-antibody ratio of eight. Following HER2 binding, the conjugate is internalized, and in lysosomes the linker is cleaved, releasing DXd, which induces DNA damage and apoptosis in tumor cells [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This targeted cytotoxic design underpins its therapeutic potency but also contributes to its distinct adverse event profile.\u003c/p\u003e\u003cp\u003eInitially approved for unresectable or metastatic HER2-positive breast cancer post prior anti-HER2 therapy, Enhertu\u0026rsquo;s indications have expanded to include HER2-low and HER2-ultralow breast cancers, both hormone receptor\u0026ndash;positive and negative, in patients exposed to endocrine or chemotherapy regimens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These broadening indications reflect its efficacy across varying levels of HER2 expression, expanding its clinical applicability [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eInterstitial lung disease (ILD), including cryptogenic organizing pneumonia (COP), is a notable and potentially fatal adverse effect of Enhertu. This risk emerged in early clinical trials and has since been validated in pooled safety data. ILD affects approximately 12% of treated patients (at the 5.4 mg/kg dose), typically presenting around a median of 5.5 months into therapy, with fatal outcomes in approximately 0.9% of cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Pooled analyses further identified risk factors such as older age, baseline lung disease, and Japanese ethnicity [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe underlying pathophysiology of T-DxD\u0026ndash;associated ILD remains incompletely elucidated. Leading hypotheses involve direct pulmonary toxicity from off-target DXd deposition, immune-mediated inflammatory injury, and bystander effects due to the payload\u0026rsquo;s membrane permeability and high drug-to-antibody ratio [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Broader reviews of drug-induced ILD emphasize immune dysregulation, oxidative stress, and alveolar epithelial injury as convergent mechanisms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImaging, notably high-resolution computed tomography (HRCT), is crucial for timely diagnosis and monitoring of Enhertu-related ILD. HRCT excels in detecting ground-glass opacities, consolidations, and perilobular patterns indicative of COP. In multicenter studies, COP was the most common radiographic pattern (72%), with mixed OP/hypersensitivity pneumonitis (HP), acute interstitial pneumonia/ARDS, and pure HP also reported [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A recent multicenter analysis further detailed correlations between imaging phenotypes and clinical outcomes, underscoring HRCT\u0026rsquo;s role in guiding both diagnosis and prognosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinical manifestations of Enhertu-associated ILD span a spectrum from asymptomatic, incidentally detected grade 1 findings to life-threatening grade 5 pneumonitis. Grade 1 ILD is managed by interrupting therapy until resolution (with or without corticosteroids), potentially allowing rechallenge at the same or reduced dose. In contrast, grade 2 or higher mandates permanent discontinuation and immediate initiation of systemic corticosteroids (e.g., prednisolone\u0026thinsp;\u0026ge;\u0026thinsp;1 mg/kg/day) with gradual tapering over at least four weeks [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Expert consensus now emphasizes baseline pulmonary evaluation, proactive HRCT surveillance, and early corticosteroid initiation as best practices [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Select case series demonstrate successful rechallenge after full recovery under rigorous clinical and imaging monitoring [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn summary, trastuzumab deruxtecan constitutes a significant therapeutic advance in HER2-targeted oncology, effectively extending options across the HER2 expression continuum [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, its association with ILD\u0026mdash;most commonly manifesting with COP patterns\u0026mdash;necessitates vigilant surveillance, patient education, and structured management protocols. Early detection via HRCT, prompt intervention, and individualized decision-making are essential to maximize clinical benefit while minimizing morbidity and mortality.\u003c/p\u003e\u003cp\u003eprotocols. Early detection via HRCT, prompt intervention, and individualized decision-making are essential to maximize clinical benefit while minimizing morbidity and mortality.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe family of the patient has provided written informed consent for the publication of their case details and any related images. Approval for this case report was not required to secure from the Ethics Committee of the institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the family of the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this case report are included within the article. Additional information is available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. No software code was used in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLisanwork Mikiyas Kebede: Writing– original draft of the manuscript, review \u0026amp; editing, Coneceptualization, Visualization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYidnekachew Demssis Awoke: Writing– review \u0026amp; editing, Data curation, Resources.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHana Genene Ruga:\u0026nbsp;Writing– review \u0026amp; editing, Data curation.\u003c/p\u003e\n\u003cp\u003eFeruza Mahmud Mehammed \u0026nbsp; : Writing– review \u0026amp; editing, Data curation.\u003c/p\u003e\n\u003cp\u003eEdelawit Tasena Noza: \u0026nbsp; \u0026nbsp;Writing– review \u0026amp; editing, Data curation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor’s Information\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eName\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEmail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInstitution\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLisanwork Mikiyas Kebede\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\[email protected]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLancet General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;Yidnekachew Demssis Awoke\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\[email protected]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLancet General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHana Genene Ruga\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\[email protected]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLancet General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;Feruza Mahmud Mehammed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\[email protected]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLancet General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEdelawit Tasena Noza\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\[email protected]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLancet General Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEuropean Medicines Agency. Enhertu \u0026ndash; Product Information [Internet]. 2025 [cited 2025 Aug 11].Availablefrom:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ema.europa.eu/en/documents/product-information/enhertu-epar-product-information_en.pdf\u003c/span\u003e\u003cspan address=\"https://www.ema.europa.eu/en/documents/product-information/enhertu-epar-product-information_en.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eU.S. Food and Drug Administration. 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Lancet Oncol. 2023;24(4):451\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEnhertu HCP Site. Managing ILD/Pneumonitis [Internet]. 2025 [cited 2025 Aug 11]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.enhertuhcp.com/en/managing-adverse-reactions/interstitial-lung-disease-pneumonitis\u003c/span\u003e\u003cspan address=\"https://www.enhertuhcp.com/en/managing-adverse-reactions/interstitial-lung-disease-pneumonitis\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, et al. Risk factors for interstitial lung disease induced by trastuzumab deruxtecan: pooled analysis from clinical trials. 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Radiol Case Rep. 2023;18(4):1021\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEnomoto Y, Yamazaki K, Ikeda S, Fujimoto K, Ogura T, Tazawa R, et al. Post-marketing surveillance: clinical and imaging features of trastuzumab deruxtecan\u0026ndash;related ILD in Japan. Int J Clin Oncol. 2023;28(11):2125\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNagai H, Muro K, Horiike A, Matsumoto T, Nishino M, Kato T, et al. Imaging characteristics and clinical outcomes of trastuzumab deruxtecan\u0026ndash;related pneumonitis: a multicenter study. Eur J Cancer. 2023;184:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMedscape. Enhertu (trastuzumab deruxtecan) dosing and ILD guidelines [Internet]. 2025 [cited 2025 Aug 11]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://reference.medscape.com/drug/enhertu-trastuzumab-deruxtecan-4000032\u003c/span\u003e\u003cspan address=\"https://reference.medscape.com/drug/enhertu-trastuzumab-deruxtecan-4000032\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJerusalem G, Park YH, Yamashita T, Kim S-B, Tamura K, Hamilton E, et al. Management of trastuzumab deruxtecan\u0026ndash;associated interstitial lung disease: expert consensus and guidelines. ESMO Open. 2023;8(3):100782.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNakagawa K, Tsurutani J, Takahashi S, Yamaguchi K, Toyama T, Iwata H, et al. Rechallenge with trastuzumab deruxtecan after resolution of drug-induced ILD: outcomes from case series. J Thorac Oncol. 2024;19(2):195\u0026ndash;203.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bulletin-of-the-national-research-centre","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnrc","sideBox":"Learn more about [Bulletin of the National Research Centre](https://BNRC.springeropen.com)","snPcode":"42269","submissionUrl":"https://submission.springernature.com/new-submission/42269/3","title":"Bulletin of the National Research Centre","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7868590/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7868590/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTrastuzumab deruxtecan (T-DxD, Enhertu) is a HER2-directed antibody\u0026ndash;drug conjugate that has expanded treatment options for patients with HER2-positive and HER2-low breast cancer. However, its use is associated with interstitial lung disease (ILD), most commonly manifesting as cryptogenic organizing pneumonia (COP), which can be life-threatening. We present the case of a 41-year-old woman with a history of invasive ductal carcinoma of the breast who developed acute dyspnea one week after her first dose of Enhertu. High-resolution chest computed tomography revealed radiographic features consistent with organizing pneumonia, along with metastatic disease and left hemidiaphragm paralysis. This case highlights the critical importance of early recognition and management of Enhertu-induced ILD. A review of the literature underscores the need for vigilant surveillance, timely imaging, and prompt initiation of corticosteroid therapy to mitigate morbidity and mortality. Enhertu represents a major therapeutic advance, but its pulmonary toxicity necessitates a structured, multidisciplinary approach to patient monitoring and care.\u003c/p\u003e","manuscriptTitle":"Enhertu-Induced Cryptogenic Organizing Pneumonia: Case Report and Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-03 09:39:05","doi":"10.21203/rs.3.rs-7868590/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-29T10:32:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-26T12:59:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"237822237199538859769291192611126544913","date":"2025-12-18T21:30:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-13T00:28:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239299844155308751347414191322561320324","date":"2025-12-12T04:33:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-21T16:57:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-16T13:21:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-16T05:50:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bulletin of the National Research Centre","date":"2025-10-15T13:11:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bulletin-of-the-national-research-centre","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnrc","sideBox":"Learn more about [Bulletin of the National Research Centre](https://BNRC.springeropen.com)","snPcode":"42269","submissionUrl":"https://submission.springernature.com/new-submission/42269/3","title":"Bulletin of the National Research Centre","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aa2d4e65-96bd-438c-8421-103eaaad7b27","owner":[],"postedDate":"November 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:10:19+00:00","versionOfRecord":{"articleIdentity":"rs-7868590","link":"https://doi.org/10.1186/s42269-026-01414-x","journal":{"identity":"bulletin-of-the-national-research-centre","isVorOnly":false,"title":"Bulletin of the National Research Centre"},"publishedOn":"2026-02-26 15:59:38","publishedOnDateReadable":"February 26th, 2026"},"versionCreatedAt":"2025-11-03 09:39:05","video":"","vorDoi":"10.1186/s42269-026-01414-x","vorDoiUrl":"https://doi.org/10.1186/s42269-026-01414-x","workflowStages":[]},"version":"v1","identity":"rs-7868590","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7868590","identity":"rs-7868590","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}