Abstract
Introduction
Primary breast lymphoma (PBL) is a rare subtype of non-Hodgkin lymphoma (NHL), accounting for less than 0.5% of all breast malignancies. Breast lymphoma may develop in breast cancer survivors, particularly after radiotherapy, raising concerns about a treatment-related toxicity. Limited data exist regarding clinical characteristics, management, and outcomes of pts with PBL, especially amongst ethnically diverse populations. This study aims to characterize patients (pts) with PBL, including those with a prior history of breast cancer. Additionally, we explore outcomes in the Hispanic population, an area that is underrepresented in clinical trials and the medical literature.
Methods
We conducted a retrospective analysis of 11 pts aged ≥18 years diagnosed with PBL between January 2015 and June 2025 at Mount Sinai Medical Center in Miami Beach, Florida. Data on demographics, tumor characteristics, treatment, and outcomes were collected through an IRB-approved chart review. Lymphomas were classified according to the World Health Organization criteria. Descriptive statistics were used to summarize patient and disease characteristics. Survival outcomes were estimated using the Kaplan-Meier method.
Results
All 11 pts were female with a median age of 70 (range 55–75): 4 (36%) were Hispanics, 5 (45%) were non-Hispanic and 2 (18%) had unknown ethnicity.
Five pts had a prior breast cancer diagnosis (1 ER/PR- and HER2+, 2 ER/PR+ and HER2-, 2 unknown), 4/5 developed lymphoma in the contralateral breast. Breast cancer therapy included: radiotherapy (4 pts), hormone therapy (2), chemotherapy (2), brachytherapy (1). The only patient that did not receive radiotherapy had longer overall survival (OS) (74.6 months) compared to the other groups (24.6, 9.9, 38.6, and 3.3 months). PBL was diagnosed after initial breast cancer diagnosis after a median of 15 years (range 9–18).
BI-RADS≥4 was reported in 8 pts (73%), BI-RADS 0 in 2 (18%), and BI-RADS 3 in 1 (9%). Mean tumor size was 1.97 cm (SD 0.96). Tumors occurred in the left breast (6 cases), right breast (4 cases), and bilateral (1 case). The histology at the time of the PBL diagnosis was heterogeneous and included 3 diffuse large B-cell lymphoma (DLBCL), 1 chronic lymphocytic leukemia that had transformed to DLBCL, 1 Burkitt's, 3 marginal zone lymphoma (MZL), 1 follicular, 1 mantle cell, and 1 lymphoplasmacytic lymphoma. No breast implant-associated anaplastic large cell lymphoma was seen including the 4 pts that underwent implant reconstruction.
PBL management included radiotherapy in 5 pts (2 pts with concomitant Rituximab and 1 with R-CHOP), and chemoimmunotherapy alone in 3 pts (1 Hyper-CVAD and 2 R-CHOP). Three pts did not require immediate therapy: 2 pts continue active surveillance after a median of 16.5 months (9-24), and 1 pt started therapy after transforming to DLBCL from MZL 42 months after the initial PBL diagnosis. Two pts failed initial therapy: one experienced progression with secondary central nervous system involvement, and the other had refractory Richter's transformation from CLL (s/p multiple treatments including axicabtagene ciloleucel). Both pts died from disease progression.
With a median follow-up of 68.4 months, the overall response rate was 64%. OS was 89% at 2 years and 76% at 5 years. The relapse rate was 45.5%, 50% in the Hispanic subgroup, suggesting a potentially higher rate of relapse within the Hispanic population. In univariate analysis for OS, normal lactate dehydrogenase levels (OR=0.74, 95% CI: 0.19–0.98) and DLBCL subtype (OR=0.94, 95% CI: 0.85–0.99) demonstrated a modest but statistically significant association with improved survival.
Conclusion
This single-center study highlights the rarity and complexity of PBL, particularly in pts of diverse backgrounds. Despite our small numbers, these findings emphasize the need for continued surveillance in long-term breast cancer survivors. PBL diagnosis remains challenging since it shares radiological characteristics with carcinoma and other more common breast pathologies. While most pts experience favorable outcomes, aggressive subtypes like Richter's transformation demand intensive therapeutic regimens and early referral to centers with clinical trial access. Our findings contribute to the limited literature on breast lymphoma and underscore the importance of tailored monitoring of Hispanic pts as well as breast cancer survivors. Larger multi-center studies are needed to confirm our findings.
