{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T08:14:31Z","timestamp":1788077671649,"version":"build-2784847793"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ministry of Health & Welfare, Republic of Korea","award":["RS-2023-KH139140 (HF23C0030)"],"award-info":[{"award-number":["RS-2023-KH139140 (HF23C0030)"]}]},{"name":"LB Abnoba Co., Ltd"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Integr Cancer Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Although pembrolizumab has shown clinical benefit in triple-negative breast cancer (TNBC), effective long-term responses remain limited.\n                    <jats:italic toggle=\"yes\">Viscum album<\/jats:italic>\n                    (mistletoe extracts, VA) may have immunomodulatory, pro-apoptotic, and immune-stimulating effects in preclinical and clinical studies. This trial was designed to evaluate the immunologic effects and safety of combining pembrolizumab with VA in the adjuvant setting. This open-label, randomized, clinical trial will include 40 adults (\u226519 years) with histologically confirmed TNBC who have undergone surgery and started adjuvant pembrolizumab but received adjuvant pembrolizumab no more than three cycles. Participants will be randomized 1:1 to receive pembrolizumab plus\n                    <jats:italic toggle=\"yes\">Viscum album<\/jats:italic>\n                    (VA group, n = 20) or to the wait-list group (n = 20). VA will be administered subcutaneously in escalating doses for 18 weeks. The primary endpoint will be the change in immune-related markers (e.g., interferon gamma, tumor necrosis factor-alpha, interleukin [IL]-2, IL-12, IL-15) assessed at baseline and weeks 4, 7, and 19. Secondary endpoints will include quality of life and safety. This ongoing study will explore whether the addition of VA enhances systemic immune activation, as reflected by cytokine modulation, and improves patient-reported quality of life without increasing adverse events. The integration of VA with pembrolizumab may offer synergistic benefits by augmenting immune responses within the tumor microenvironment. This trial is expected to generate clinical evidence regarding the immunologic implications, safety, and feasibility of this combined regimen, informing future strategies for adjuvant treatment of TNBC. The trial has been registered at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">https:\/\/ClinicalTrials.gov<\/jats:ext-link>\n                    (registration identifier: NCT06920810).\n                  <\/jats:p>","DOI":"10.1177\/15347354261483616","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:36:41Z","timestamp":1787834201000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of\n                    <i>Viscum album L.<\/i>\n                    in Patients With Triple-Negative Breast Cancer Receiving Immune Checkpoint Inhibitors: A Protocol for an Open-Label Randomized Clinical Trial"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-1915","authenticated-orcid":false,"given":"Jee Young","family":"Lee","sequence":"first","affiliation":[{"name":"CHA Ilsan Medical Center"},{"name":"CHA University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ju","family":"Ko","sequence":"additional","affiliation":[{"name":"CHA Ilsan Medical Center"},{"name":"CHA University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"CHA Ilsan Medical Center"},{"name":"CHA University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-8309","authenticated-orcid":false,"given":"Sung Eun","family":"Hong","sequence":"additional","affiliation":[{"name":"CHA Ilsan Medical Center"},{"name":"CHA University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-5676","authenticated-orcid":false,"given":"Myung Han","family":"Hyun","sequence":"additional","affiliation":[{"name":"CHA Ilsan Medical Center"},{"name":"CHA University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2011-S1-61"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S86105"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910549"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112651"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2409932"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2015.05.028"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1534735420917211"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-016-1246-2"},{"issue":"3","key":"e_1_3_7_12_2","first-page":"555815","article-title":"Successful treatment by mistletoe Viscum album extract of a patient with recurrent triple negative breast cancer who declined chemotherapy","volume":"11","author":"Parameswara VK","year":"2021","unstructured":"Parameswara VK, Hancock MJ. Successful treatment by mistletoe Viscum album extract of a patient with recurrent triple negative breast cancer who declined chemotherapy. 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