{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T03:58:40Z","timestamp":1766894320576,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Leptomeningeal metastasis (LM) is a rare and challenging manifestation of advanced breast cancer (ABC) with severe morbidity and mortality. Patients with LM may be asymptomatic, or present with non-specific neurologic deficits, thereby possibly delaying diagnosis. Treatment typically requires a multimodal approach for effective management, symptom relief, and quality-of-life improvement. Trastuzumab-deruxtecan (T-DXd), a humanized monoclonal antibody drug conjugate, demonstrated efficacy across diverse breast cancer subtypes expressing variable levels of HER2 proteins. Currently, T-DXd is the standard of care for patients with advanced, pretreated, HER2 low breast cancer. There is limited evidence of the response of brain metastases (BM) and leptomeningeal metastases (LM) to T-DXd in HER2-low patients, with most data extrapolated from HER2-positive breast cancer studies. This case report presents the first documented instance of a patient with debilitating, symptomatic, untreated LM and hydrocephalus demonstrating a rapid and dramatic clinical response to T-DXd. This finding holds crucial clinical relevance, highlighting the potential benefit of initiating effective systemic therapy for LM early in treatment to address both central nervous system (CNS) and non-CNS disease burden, rather than delaying systemic therapy until after radiation therapy.<\/jats:p>","DOI":"10.3390\/curroncol32020081","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:42:36Z","timestamp":1738305756000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Dramatic Clinical Response to Trastuzumab-Deruxtecan in a Patient with HER-2 Low Breast Cancer with Untreated Leptomeningeal Metastasis and Hydrocephalus"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1400-8735","authenticated-orcid":false,"given":"Sarah","family":"Hussain","sequence":"first","affiliation":[{"name":"Arthur Child Comprehensive Cancer Center, Calgary, AB T2N 5G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Nordal","sequence":"additional","affiliation":[{"name":"Arthur Child Comprehensive Cancer Center, Calgary, AB T2N 5G2, Canada"},{"name":"Department of Radiology, Foothills Medical Center, Calgary, AB T2N 2T9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"Willson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Foothills Medical Center, Calgary, AB T2N 2T9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-8198","authenticated-orcid":false,"given":"Xiaolan","family":"Feng","sequence":"additional","affiliation":[{"name":"Arthur Child Comprehensive Cancer Center, Calgary, AB T2N 5G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7573\/dic.2021-6-6","article-title":"Leptomeningeal carcinomatosis and breast cancer: A systematic review of current evidence on diagnosis, treatment and prognosis","volume":"10","author":"Mollica","year":"2021","journal-title":"Drugs Context"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3892\/ol.2016.4745","article-title":"Leptomeningeal carcinomatosis as the primary presentation of relapse in breast cancer","volume":"12","author":"Sacco","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/jso.2930480106","article-title":"Metastatic pattern of infiltrating lobular carcinoma of the breast: An autopsy study","volume":"48","author":"Lamovec","year":"1991","journal-title":"J. Surg. Oncol."},{"key":"ref_4","first-page":"1177","article-title":"Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer","volume":"8","author":"Tarantino","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1007\/s12282-022-01364-y","article-title":"Prognostic values of clinical and molecular features in HER2 low-breast cancer with hormonal receptor overexpression: Features of HER2-low breast cancer","volume":"29","author":"Chen","year":"2022","journal-title":"Breast Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF02341153","article-title":"Leptomeningeal metastases: Comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias","volume":"9","author":"Kaplan","year":"1990","journal-title":"J. Neurooncol."},{"key":"ref_7","first-page":"iv84","article-title":"EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours","volume":"28","author":"Weller","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ferguson, S.D., Fomchenko, E.I., Guerrieri, R.A., and Glitza Oliva, I.C. (2022). Challenges and advances in diagnosis and treatment of leptomeningeal disease (LMD). Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.800053"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1200\/JCO.21.02314","article-title":"Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline","volume":"40","author":"Vogelbaum","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1177\/107327481702400107","article-title":"Surgical treatment for leptomeningeal disease","volume":"24","author":"Volkov","year":"2017","journal-title":"Cancer Control."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-019-6228-6","article-title":"Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer","volume":"19","author":"Bazan","year":"2019","journal-title":"BMC Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1215\/S1152851703000334","article-title":"Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy","volume":"6","author":"Rogers","year":"2004","journal-title":"Neuro. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/1078-0432.CCR-22-1138","article-title":"Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases","volume":"29","author":"Kabraji","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kubeczko, M., Jarz\u0105b, M., Krzywon, A., Gr\u00e4upner, D., Polakiewicz-Gilowska, A., and Gabry\u015b, D. (2023). Efficacy of CDK 4\/6 inhibitors and radiotherapy in breast cancer patients with brain metastases. J. Clin. Med., 12.","DOI":"10.3390\/jcm12052044"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"CNS65","DOI":"10.2217\/cns-2020-0023","article-title":"Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: A comprehensive review","volume":"9","author":"Fernandes","year":"2020","journal-title":"CNS Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.breast.2020.11.019","article-title":"Complete response of leptomeningeal carcinomatosis secondary to breast cancer","volume":"54","author":"Troussier","year":"2020","journal-title":"Breast"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1007\/s12282-024-01600-7","article-title":"Trastuzumab deruxtecan versus treatment of physician\u2019s choice in previously treated Asian patients with HER2-low unresectable\/metastatic breast cancer: Subgroup analysis of the DESTINY-Breast04 study","volume":"31","author":"Yamashita","year":"2024","journal-title":"Breast Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.annonc.2023.12.001","article-title":"Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: Updated survival results from a phase II trial (DESTINY-Breast01)","volume":"35","author":"Saura","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(23)00725-0","article-title":"Trastuzumab deruxtecan versus treatment of physician\u2019s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): A randomised, open-label, multicentre, phase 3 trial","volume":"401","author":"Kim","year":"2023","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1038\/s41591-024-03021-7","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: Long-term survival analysis of the DESTINY-Breast03 trial","volume":"30","author":"Hurvitz","year":"2024","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"TPS1096","DOI":"10.1200\/JCO.2021.39.15_suppl.TPS1096","article-title":"Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: A phase 1b\/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07)","volume":"39","author":"Hamilton","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.annonc.2024.08.2347","article-title":"A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases","volume":"35","author":"Curigliano","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_23","unstructured":"ESMO Daily Reporter (2024, October 14). Antibody-Drug Conjugates Offer Hope for Breast Cancer Patients. Available online: https:\/\/dailyreporter.esmo.org\/esmo-congress-2024\/breast-cancer\/antibody-drug-conjugates-offer-hope-for-patients-with-breast-cancer-including-patients-with-brain-metastases."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1038\/s41591-023-02478-2","article-title":"Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: The phase 2 DAISY trial","volume":"29","author":"Mosele","year":"2023","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/neuonc\/noae123","article-title":"Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases","volume":"26","author":"Bartsch","year":"2024","journal-title":"Neuro Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41523-023-00519-0","article-title":"Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan","volume":"9","author":"Alder","year":"2023","journal-title":"NPJ Breast Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/neuonc\/noac144","article-title":"Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial","volume":"25","author":"Cortez","year":"2023","journal-title":"Neuro Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41523-023-00584-5","article-title":"Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and\/or leptomeningeal disease (ROSET-BM)","volume":"9","author":"Niikura","year":"2023","journal-title":"NPJ Breast Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1200\/OP.22.00480","article-title":"Real-world perspectives and practices for pneumonitis\/interstitial lung disease associated with trastuzumab deruxtecan use in human epidermal growth factor receptor 2-expressing metastatic breast cancer","volume":"19","author":"Rugo","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1159\/000534572","article-title":"Response of brain and meningeal metastases to trastuzumab-deruxtecan in a patient with her2-low breast cancer: A case report","volume":"16","author":"Wolf","year":"2023","journal-title":"Case Rep. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1200\/JCO.22.01148","article-title":"Randomized phase II trial of proton craniospinal irradiation versus photon involved-field radiotherapy for patients with solid tumor leptomeningeal metastasis","volume":"40","author":"Yang","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Perlow, H.K., Matsui, J.K., Ewing, A., Cadieux, C., Blakaj, D.M., Beyer, S., Thomas, E.M., Grecula, J.C., Raval, R., and Palmer, J.D. (2023). Volumetric modulated arc therapy craniospinal irradiation utilizing a vertebral body sparing approach: A toxicity analysis. Int. J. Radiat. Oncol. Biol. Phys., 117.","DOI":"10.1016\/j.ijrobp.2023.06.642"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/2\/81\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:24:51Z","timestamp":1760027091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/2\/81"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["curroncol32020081"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32020081","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}