Background: The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. Methods: We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Results: Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0.001). Conclusions: Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

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Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, offering a highly personalized and potent immunotherapeutic approach. To date, the U.S. Food and Drug Administration has approved seven CAR-T therapies targeting CD19 and B-cell maturation antigen; each demonstrated remarkable clinical efficacy across various hematologic malignancies. Despite significant advancements in preclinical studies and clinical trials, no CAR-T therapy has been approved for solid tumors, which account for the majority of cancer cases worldwide. These key challenges include the lack of distinct and accessible target antigens, the immunosuppressive tumor microenvironment (TME) that impairs immune cell efficacy, the heterogeneity of solid tumors that complicates treatment uniformity, and the potential risks of off-tumor toxicity. These obstacles represent a complex array of biological and clinical obstacles, distinct from the more favorable immune environment of hematologic cancers that has been pivotal to the success of CAR-T therapy. Preclinical studies in multiple myeloma emphasize memory T-cell optimization and combinatorial strategies to enhance CAR-T efficacy in solid tumors. Our review emphasizes innovative strategies to address these key challenges in CAR-T therapy for solid tumors, including advanced multi-antigen targeting approaches, reprogramming of the TME, and the development of next-generation safety measures to mitigate toxicity risks. By addressing both scientific and clinical obstacles, this review envisions a future in which CAR-T therapy’s full potential extends beyond hematologic malignancies, transforming the landscape of oncology and improving outcomes for patients with solid tumors.