Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

Abstract

Background Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. Methods We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6–56.8%) and 37.5% (95% CI, 24.0–52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

Primary Diffuse Large B-Cell Lymphoma of the Breast with MYC and BCL2 Rearrangements with Terminal Deoxynucleotidyl Transferase Expression: A Case Report

“…Oki et al OS after first progression was poor even after salvage stem cell transplant (SCT) (3yOS 15% vs. 7%). Albeit, SCT is an option for the treatment of DLBCL with MYC and BCL2 rearrangement, with same prognosis if done after first complete remission or after a second line of treatment with complete response [2] and less CNS progression (p < 0.001). So SCT is generally recommended to reduce CNS relapse rate.…”

“…Primary breast lymphoma represents 1% of non-Hodgkin lymphomas and 2% of all extra nodal lymphomas [1]. The most common histologic type is diffuse large B-cell lymphoma (DLBCL) representing 60-85% of cases, followed by marginal zone lymphoma in 16% of cases and follicular lymphoma in 5.4% of cases with rare cases of Burkitt's lymphoma and Hodgkin lymphoma described in the literature [1][2][3].…”

“…The most common presentation of primary breast lymphoma is a unilateral painless breast mass in a middle age woman, but in up to 11% of cases, it can present bilaterally [ 2 ]. Large B-cell lymphomas with translocation of MYC and BCL2 and/or BCL6 as detected by FISH are known as “double hit” lymphomas (DHL) with the vast majority being germinal center B-like lymphomas classified as high-grade lymphoma in the World Health Organization WHO 2016.…”

A Rare Case of Primary Breast Diffuse Large B-cell Lymphoma in an Acquired Immunodeficiency Syndrome Patient

“…A retrospective Surveillance, Epidemiology, and End Results (SEER) database analysis demonstrated that patients treated with systemic regimens including rituximab followed by radiation therapy had a significantly greater five-year overall survival (OS) compared to those that did not receive radiotherapy [ 12 ]. A retrospective analysis on a limited number of patients demonstrated that treatment with dose-adjusted EPOCH-rituximab, alternating with high-dose methotrexate and cytarabine had a higher five-year OS compared to two other regimens [ 14 ]. Presently, no definitive guidelines exist for primary breast DLBCL.…”

The prognostic value of IPI in patients with primary breast lymphoma, a multicenter retrospective study

“…By reviewing the relevant literature, we found the present clinical issue, that the prognostic value of IPI in PBL is controversial. Studies by Ryan et al [ 6 ], Hu et al [ 9 ], Zhang et al [ 34 ], Shao et al [ 15 ], Yhim et al [ 35 ] demonstrated that the IPI scores were independent risk factors for PFS and OS, while results from Zhao et al [ 36 ], Qu et al [ 37 ] and Zhang et al [ 38 ] confirmed that the IPI scores were not associated with PFS and OS in PBL. The result was presented in the forest graph format (Fig.…”