{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:22:54Z","timestamp":1787376174551,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>This study evaluated clinical characteristics, treatment outcomes, and CNS relapse patterns in patients with breast-involved diffuse large B-cell lymphoma (DLBCL), a rare extranodal presentation with limited real-world data. We conducted a retrospective study on 33 consecutive patients with newly diagnosed breast-involved DLBCL treated from 2019 to 2024. All patients received R-CHOP. Baseline CNS screening\u2014including neurological examination, fundoscopy, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis\u2014was routinely performed. High-dose methotrexate (HD-MTX) was offered as CNS prophylaxis after completion of systemic therapy based on multidisciplinary team evaluation and clinician\u2013patient shared decision-making according to institutional treatment protocols. Median age was 52.6 years; 84.8% had ECOG 0. Non-GCB subtype predominated (84.8%), and Ki-67 &gt;70% was present in 69.7%. The overall response rate was 90.9%, with 84.8% complete responses. At a median follow-up of 44 months, 5-year Overall Survival (OS) and Progression-Free Survival (PFS) were 84.8% and 66.7%. CNS relapse occurred in 4 of 6 patients (66.7%) without prophylaxis, all within 5\u201311 months after R-CHOP, whereas no CNS relapses were observed among prophylaxis recipients (p &lt; 0.001), although this observation should be interpreted with extreme caution given the very small non-prophylaxis subgroup (n = 6), limited statistical power, and non-randomized treatment allocation. Exploratory analyses suggested that bulky disease was associated with inferior OS. R-CHOP achieved high response rates and favorable long-term outcomes in breast-involved DLBCL. The absence of CNS relapse among HD-MTX prophylaxis recipients, contrasted with a high relapse rate in those without prophylaxis, provides only a hypothesis-generating observation that requires confirmation in larger prospective studies; this warrants further investigation of the role of systemic CNS prophylaxis.<\/jats:p>","DOI":"10.3390\/curroncol33080493","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Outcomes of Breast-Involved Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Real-World Study with Insights into CNS Prophylaxis"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4427-9707","authenticated-orcid":false,"given":"Thi Thu Huong","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Oncology, Hanoi Medical University, Hanoi 100000, Vietnam"},{"name":"Department of Quan Su Medical Oncology, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Yen","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Quan Su Medical Oncology, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5271-9738","authenticated-orcid":false,"given":"Thanh Tung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology No. 7, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0601-1013","authenticated-orcid":false,"given":"Thanh Long","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology No. 6, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5563-9672","authenticated-orcid":false,"given":"Xuan Dai","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan Anh","family":"Pham","sequence":"additional","affiliation":[{"name":"Department A, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Tu","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Tam Hiep Medical Oncology, Vietnam National Cancer Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thanh Ha","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Thanh Hoa Oncology Hospital, Thanh Hoa 440000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Quang","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1093\/annonc\/mdt192","article-title":"Primary diffuse large B-cell lymphoma of the breast: Looking at pathogenesis, clinical issues and therapeutic options","volume":"24","author":"Aviv","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.18632\/oncotarget.23285","article-title":"Primary breast diffuse large B-cell lymphoma: A population-based study from 1975 to 2014","volume":"9","author":"Jia","year":"2018","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1259\/bjr\/78413721","article-title":"Primary and secondary breast lymphoma: Prevalence, clinical signs and radiological features","volume":"85","author":"Surov","year":"2012","journal-title":"Br. J. Radiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1148\/rg.2019180097","article-title":"Primary and Secondary Breast Lymphoma: Clinical, Pathologic, and Multimodality Imaging Review","volume":"39","author":"Raj","year":"2019","journal-title":"RadioGraphics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jpra.2022.01.004","article-title":"Primary Lymphomas of the Breast: A Review","volume":"32","author":"James","year":"2022","journal-title":"JPRAS Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1097\/01.sla.0000254418.90192.59","article-title":"Primary breast lymphoma: The role of mastectomy and the importance of lymph node status","volume":"245","author":"Jennings","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_7","unstructured":"National Comprehensive Cancer Network (B-Cell Lymphomas, 2026). B-Cell Lymphomas, Version 03.2026."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S272","DOI":"10.21037\/tcr.2017.11.10","article-title":"Diagnosis and management of breast lymphoma: A single- institution retrospective analysis","volume":"7","author":"Orlandi","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1159\/000088333","article-title":"Primary breast lymphoma: Results of a controlled clinical trial","volume":"69","author":"Delgado","year":"2005","journal-title":"Oncology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/annonc\/mdh013","article-title":"Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: Influence of rituximab","volume":"15","author":"Feugier","year":"2004","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/annonc\/mdm471","article-title":"Primary diffuse large B-cell lymphoma of the breast: Prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group","volume":"19","author":"Ryan","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1349-7006.2011.02139.x","article-title":"Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era","volume":"103","author":"Tomita","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1093\/annonc\/mdp432","article-title":"Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: The impact of the addition of rituximab to CHOP chemotherapy","volume":"21","author":"Villa","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1056\/NEJMoa011795","article-title":"CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma","volume":"346","author":"Coiffier","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1182\/blood-2010-03-276246","article-title":"Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d\u2019Etudes des Lymphomes de l\u2019Adulte","volume":"116","author":"Coiffier","year":"2010","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S1470-2045(11)70235-2","article-title":"CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group","volume":"12","author":"Pfreundschuh","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154","DOI":"10.2325\/jbcs.12.154","article-title":"Primary non-Hodgkin\u2019s lymphoma of the breast: Report of a case with special reference to 380 cases in the Japanese literature","volume":"12","author":"Uesato","year":"2005","journal-title":"Breast Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yhim, H.-Y., Kang, H.J., Choi, Y.H., Kim, S.J., Kim, W.S., Chae, Y.S., Kim, J.S., Choi, C.W., Oh, S.Y., and Eom, H.S. (2010). Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-321"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1097\/PAS.0b013e318165eb50","article-title":"Lymphomas involving the breast: A study of 106 cases comparing localized and disseminated neoplasms","volume":"32","author":"Talwalkar","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/00000478-199403000-00009","article-title":"Non-Hodgkin\u2019s lymphoma involving the breast","volume":"18","author":"Arber","year":"1994","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/00000421-199908000-00011","article-title":"Primary lymphoma of the breast: Breast mass as an initial symptom","volume":"22","author":"Kim","year":"1999","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/modpathol.3800266","article-title":"Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype","volume":"18","author":"Yoshida","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.leukres.2008.04.005","article-title":"Clinicopathologic features and treatment outcome of primary breast diffuse large B-cell lymphoma","volume":"32","author":"Niitsu","year":"2008","journal-title":"Leuk. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Maher, N., Maiellaro, F., Ghanej, J., Rasi, S., Moia, R., and Gaidano, G. (2025). Unraveling the Epigenetic Landscape of Mature B Cell Neoplasia: Mechanisms, Biomarkers, and Therapeutic Opportunities. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178132"},{"key":"ref_26","first-page":"100468","article-title":"Seroprevalence of Hepatitis B, C and D in Vietnam: A systematic review and meta-analysis","volume":"24","author":"Flower","year":"2022","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wilson, M.R., Lewis, K.L., Kirkwood, A.A., Cwynarski, K., Cheah, C.Y., El-Galaly, T.C., Villa, D., Savage, K.J., Ghione, P., and Bobillo, S. (2026). High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis. J. Clin. Oncol.","DOI":"10.1200\/JCO-26-01800"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3816\/CLM.2006.n.010","article-title":"Primary non-Hodgkin\u2019s lymphoma of the breast: Retrospective analysis of prognosis and patterns of failure in two Australian centers","volume":"6","author":"Ryan","year":"2006","journal-title":"Clin. Lymphoma Myeloma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa2115304","article-title":"Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma","volume":"386","author":"Tilly","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Laddaga, F.E., Della Mura, M., Sorino, J., Caruso, A., Martinotti, S., Ingravallo, G., and Gaudio, F. (2025). Sequencing Anti-CD19 Therapies in Diffuse Large B-Cell Lymphoma: From Mechanistic Insights to Clinical Strategies. Int. J. Mol. 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