Impact of Cell-of-Origin and MYC/BCL2 Status on the Risk of Central Nervous System Relapse in Primary Breast Diffuse...

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity with a distinct relapse pattern involving the central nervous system (CNS). However, data regarding predictors of CNS relapse in this population remain limited.

CNS relapse was retrospectively analyzed in two multicenter cohorts comprising 53 patients with newly diagnosed primary breast DLBCL, including a prospective trial and real-world cohort, all treated with rituximab-based immunochemotherapy. The impact of baseline clinical parameters, cell-of-origin, and MYC/BCL2 dual expression (DE) status on CNS relapse was assessed using a multivariate Cox regression model, separately conducted for the overall study set (n=53) and the immunohistochemical study set (n=36).

By the CNS-International Prognostic Index (CNS-IPI), most patients were classified as low or intermediate risk; no patients were classified as high risk. With a median follow-up of 58.8 months, the 4-year risk of CNS relapse was 15.6% in the overall study set and 14.2% in the immunohistochemical set. MYC/BCL2 DE was identified in 14 patients (38.9%) and was significantly associated with increased risk of CNS relapse (4-year risk, 30.7% vs. 0%, p=0.001). Patients with non-germinal center B-cell-like subtype had a numerically higher risk of CNS relapse. However, in multivariate analysis, only MYC/BCL2 DE status was associated with CNS relapse. Synchronous bilateral involvement was also an independent predictor of CNS relapse in both study sets. CNS-IPI was not discriminatory for CNS relapse.

MYC/BCL2 DE and synchronous bilateral breast involvement may help identify patients at higher risk for CNS relapse. Further studies are warranted.