Primary Breast Diffuse Large B-cell Research Articles

Predicting central nervous system relapse in primary breast diffuse large B-cell lymphoma using the stage-modified IPI score: A retrospective cohort study

ObjectiveThe existing Central Nervous System-International Prognostic Index (CNS-IPI) provides insufficient guidance for predicting central nervous system (CNS) relapse in individuals with primary breast diffuse large B-cell lymphoma (DLBCL). This retrospective cohort study sought to examine the potential of the stage-modified IPI in predicting CNS relapse within this specific patient population. Patients and methodsWe examined the baseline characteristics of 76 consecutive patients diagnosed with primary breast DLBCL, calculating the stage-modified IPI score for each individual. Utilizing a competing risk regression (CRR) model, we conducted both univariate and multivariate analyses to explore the relationship between potential prognostic factors and the occurrence of CNS relapse. ResultsIn our cohort, the rates of CNS disease at 2 and 5 years since the diagnosis of primary breast DLBCL are 3.9% and 7.8%, respectively. Among patients experiencing CNS relapse, 80% presented with a parenchymal brain mass. Individuals with a high stage-modified IPI score (1–3 points) had a significantly higher incidence of CNS relapse (p = 0.031), a shorter time from the initial diagnosis of primary breast DLBCL to the first CNS relapse (p = 0.010), as well as relapse at any site (p = 0.012), compared to those with a low score (0 points). Univariate analysis identified stage (Hazard Ratio (HR): 4.098, p = 0.024), stage-modified IPI score (HR: 11.582, p = 0.012), and radiation therapy (HR: 5.784, p = 0.026) as significant risk factors. In multivariate analysis, in addition to radiation therapy (HR: 7.258, p = 0.012), the stage-modified IPI score (1–3 points versus 0 points) emerged as an independent and reliable predictor for CNS relapse (HR: 12.945, p = 0.016). ConclusionOur study underscores the significance of stage-modified IPI scores in predicting CNS relapse for patients with primary breast DLBCL. Validation of these findings through further research is essential, along with exploring potential prevention and intervention approaches.

Comparative analysis of conventional ultrasound and shear wave elastography features in primary breast diffuse large B-cell lymphoma

Comparative analysis of conventional ultrasound and shear wave elastography features in primary breast diffuse large B-cell lymphoma

Clinical Features and Outcomes of Primary Breast Diffuse Large B-Cell Lymphoma: A Matched-Pair Study.

The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.

Impact of BCL2/MYC Protein Dual Expression and Other Clinical Factors on the Risk of Central Nervous System Progression in Patients with Primary Breast Diffuse Large B-Cell Lymphoma

Background Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). Recent studies have reported that cell-of-origin (COO), BCL2/MYC dual expression (DE), and MYC and BCL2 and/or BCL6 rearrangements, so-called double hit (DH) and triple hit, are associated with a high risk of CNS progression in DLBCL; however, the impact of these biologic markers in primary breast DLBCL on CNS progression remains unknown. Methods CNS progression was analyzed in newly diagnosed primary breast DLBCL patients identified from 2 sources: the prospective study of the Consortium for Improving Survival of Lymphoma (CISL) study group conducted from January 2012 to July 2017, and the retrospective cohort included patients who were treated outside clinical trial at any CISL institutions between January 2012 and December 2020. Briefly, the prospective study (Yhim HY et al. Cancers 2020;12:2192) included 33 patients (20-75 years of age) with primary breast DLBCL, and treatment consisted of 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 4 doses of intrathecal (IT) methotrexate (MTX) at a 3-week interval. The eligibility criteria for the retrospective cohort were virtually the same as the prospective cohort, except for no age limit. 26 patients were screened, 6 of whom were excluded because of incomplete data (n=4) and secondary breast DLBCL (n=2). Thus, the retrospective cohort included 20 patients treated with 6 cycles of R-CHOP ± radiotherapy. CNS prophylaxis was not considered for eligibility in this cohort but was done in 17 patients (4-6 doses of IT MTX [n=14] and systemic high-dose MTX [n=3]). Expert hematopathologists centrally assessed COO and DE status. COO was determined using the Hans algorithm. MYC (≥40%) and BCL2 (≥50%) protein expressions were used to assign DE. Fluorescence in situ hybridization testing was used to determine DH lymphoma. The risk of CNS progression was estimated using the cumulative incidence method. The impact of variables of interest on CNS progression was assessed using a multivariable Cox model. Results We identified 53 patients from 2 data sources. The median age was 55 years (range, 29-78), and all were female. Most patients had unilateral (n=50, 94%), localized-stage (n=48, 91%), and ECOG performance status ≤1 (n=51, 95%). Serum LDH level was elevated in 14 (26%). Hence, IPI and CNS-IPI risks were mainly low (n=45, 85%). No patients had CNS disease at diagnosis. With a median follow-up of 58.8 months (IQR, 30.3-72.9), 7 patients developed CNS progression (parenchymal only, n=4; leptomeningeal only, n=2; parenchymal and leptomeningeal, n=1). The 4-year cumulative incidence of CNS progression was 15.6% (95% CI, 6.7-27.9; Fig A). The Cox analysis revealed bilateral breast involvement (HR, 9.39; 95% CI, 1.69-52.18) was an independent factor for CNS progression in this population. Of the 53 patients, 36 were selected as a histologic data-available population because of a lack of diagnostic materials for COO and DE in 17 patients. Baseline characteristics of the histologic data-available population (n=36) were similar to the overall population (n=53). In the 36 patients with histologic data available, 4 patients had CNS progression (parenchymal only, n=2; leptomeningeal only, n=1; parenchymal and leptomeningeal, n=1), and the 4-year CNS progression rate was 14.2% (95% CI, 0.4-26.3; Fig B). According to the Hans algorithm, 30 (83%) and 6 (17%) were classified as having non-GCB and GCB, respectively. 14 patients (39%) had BCL2/MYC DE, of whom 13 were non-GCB subtype (Fig C). The CNS progression rate of non-GCB did not differ significantly from that of the GCB subtype (4-year, 17.4% vs. 0%; p=0.326), but BCL2/MYC DE had a higher risk of CNS progression than non-DE (4-year, 30.7% vs. 0%, p=0.021; Fig D). 20 patients had sufficient tissue to test DH status, but no DH cases were identified. The multivariable Cox analysis of these 36 patients showed bilateral involvement (HR, 3.73; 95% CI, 1.28-10.86) and BCL2/MYC DE (HR, 2.42×104; 95% CI, 0.51×104-10.60×104) were independent predictors for CNS progression. Conclusion Our data suggested that bilateral breast involvement and BCL2/MYC DE were independent risk factors for CNS events in patients with primary breast DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABCL-398 Primary Breast Diffuse Large B-Cell Lymphoma: An Indian Experience

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare site of localized extranodal DLBCL. It represents 0.5% of all primary malignant neoplasms of the breast and around 2% of extranodal lymphomas. There is a paucity of data regarding the clinicopathologic characteristics, cell of origin, response, and outcome of treatment with uniform treatment protocol in patients from India diagnosed with PB-DLBCL. This was a retrospective study of 18 consecutive cases of PB-DLBCL registered at All India Institute of Medical Sciences between 2006 and 2021 treated with uniform 3x weekly cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) ±rituximab (R) with involved-field radiotherapy. The patients were classified as germinal center B-cell-like or activated B-cell (ABC) type using the Hans classification. The median age was 43 (21-67) years with a male:female ratio of 1:17. All the patients presented with a breast lump with a median tumor size of 5 cm. The right side was involved in 11 (61.1%) cases. Eight patients were diagnosed with lumpectomy, 9 patients with biopsy, and one patient with mastectomy specimen. Out of 18 patients, Ann Arbor: Stage I was seen in 6 (33.3%) patients, Stage IIE in 11 (61.1%) patients, and Stage 1V in 1 (5.5%) patient. B-symptoms and bulky disease were seen in 6 (33.3%) and 7 (38.8%) patients, respectively. Cell of origin data were available in 14 patients, and 11 (71.4%) were ABC in origin. Low- and intermediate-risk International Prognostic Index was seen in 42% and 48% of patients, respectively. The median number of chemotherapy cycles was 4 (3-6), rituximab was used in 10 (55.5%) cases, and CNS prophylaxis with intrathecal methotrexate was used in 10 (55.5%) cases. The complete response rate was 83.3%. After a median follow-up of 42 months, the 3-year progression-free survival and overall survival were 75% and 88%, respectively. The most common site of relapse (n=3) was parenchymal brain disease. Multimodality combination therapy (chemotherapy, immunotherapy, and radiation) can give good survival with PB-DLBCL but adding high-dose methotrexate to existing protocol needs further exploration.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

BackgroundPrimary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors.Patients and MethodsA consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause.ResultsA total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25–80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4–25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3–89.5) and 84.8% (95% CI: 70.0–93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6–84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2–3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043).ConclusionIn our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Case report: Zanubrutinib-induced dermatological toxicities: A single-center experience and review

Zanubrutinib, a next-generation non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may experience a series of side effects after the treatment of zanubrutinib. Grade 4 dermatological toxicities are rare, which present as severe rash and skin infection. Herein, we retrospectively reported the grade 4 dermatological toxicities of zanubrutinib in three consecutive patients. They were treated with zanubrutinib 160 mg twice daily orally. One patient was diagnosed with Primary Breast Diffuse Large B-cell Lymphoma(PB-DLBCL) and two patients were diagnosed with Chronic Lymphocytic Leukemia(CLL). Within one month after zanubrutinib treatment, all three patients developed grade 4 dermatological toxicities, including bruising, maculopapular rash, petechiae, ecchymosis, hemorrhagic blister, acne-Like rash, papulopustular rash, and skin infections. Zanubrutinib was discontinued in two patients due to unacceptable dermatological toxicities. Safety data from pre-licensing clinical trials showed that zanubrutinib-related side effects were frequent but well tolerated. To date, no severe dermatological toxicities were reported. The majority of patients can be relieved with symptomatic treatment, but a very small percentage of patients may face discontinuation of the drug.

Spontaneous remission of primary breast diffuse large B-cell lymphoma

A 71-year-old woman became aware of a 25-mm mass in her right breast as identified by her previous doctor. Needle biopsy findings suggested malignant lymphoma, and she was referred to our hospital for further evaluation. She was diagnosed with diffuse large B-cell lymphoma (DLBCL) at our hospital. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value; 10.3), with the mass localized in the right breast, but magnetic resonance imaging findings revealed that the mass had shrunk to 10 mm. Needle biopsy was repeated in our hospital, and lymphoma cells were absent. Two months later, CT scan revealed complete disappearance of the mass, and, since then, the patient has been free of recurrence. Although there are reports of spontaneous remission of nonHodgkin's lymphoma, it is rare in the case of high-grade B-cell lymphoma. The mechanism of spontaneous remission is unclear; however, advancing age, localized stage, activated B-cell (ABC) or nongerminal center B-cell (GCB) type, and a history of infection are the associated factors. The findings from this case suggest that DLBCL can be cured without therapeutic intervention; however, careful followup may be needed.

A case of primary breast diffuse large B cell lymphoma

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin’s lymphoma with limited data. We here report a case of primary breast diffuse large B-cell lymphoma mimicking breast cancer. A 52-year-old woman had a painless mass in her right breast. Fine needle aspiration cytology and core biopsy were performed which suggested malignant features but could not confirm the specific subtype. Excisional biopsy then was conducted revealing non-Hodgkin lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and modest lymphadenopathy in the ipsilateral axilla. The patient received six courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy, then whole breast radiation (30Gy in 15 fractions). At 12 months of follow-up, the patient survives with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We briefly review the current practice pattern in patients with primary breast diffuse large B-cell lymphoma.

Metachronous Diffuse Large B-Cell Lymphoma of the Breasts: A Case Report and Review of the Literature.

Introduction: Primary breast lymphoma (PBL) is a rare form of extranodal lymphoma. The most common pathology is diffuse large B cell lymphoma and most patients are diagnosed at stages 1 and 2. The therapeutic options available so far include surgery, radiotherapy, and chemotherapy Case Presentation: The patient was a 54-year old woman with localized primary breast diffuse large B-cell lymphoma (DLBCL). The patient underwent 6 courses of chemotherapy with an R-CHOP regimen followed by radiotherapy of the breast and regional lymph nodes with a dose of 40 Gy. In PET scan done three months later, the patient was in complete remission. Around one year later, the patient experienced relapse in the contralateral breast. Conclusions: In the pattern of lapse of patients, there is a tendency for extranodal relapse. In some studies it has been speculated that there is a high probability of relapse in central nervous system (CNS) and some authorities advocate CNS prophylaxis in these patients. The best outcome would be for patients treated with chemotherapy including rituximab followed by radiation. We reviewed some studies regarding treatment modalities and site of relapse.

Primary Breast Diffuse Large B-Cell Lymphoma in a 42-Year-Old Female: A Case Report and Review of Literature

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare localized extranodal lymphoma. It is mainly diagnosed by pathological examination due to the lack of specific clinical and imaging manifestations. Whole-body positron emission tomography-computed tomography (PET-CT) is widely used in determining clinical staging and guiding clinical treatment. As part of comprehensive treatment, targeted therapy with rituximab, intrathecal methotrexate injection and consolidation radiotherapy remain controversial in treating PB-DLBCL, but the comprehensive treatment based on full-course of chemotherapy is still widely used as the first-line treatment. Comprehensive treatment often leads to a sharp decline in the immunity of elderly patients with malignancy. In this situation, surgery may be a good chance to improve their life quality without serious complications. We present a rare case of PB-DLBCL during the coronavirus disease 2019 (COVID-19) pandemic. The patient underwent chest CT scan to screen COVID-19 and a mass of left breast was accidentally found. Because of the city lockdown policy in Wuhan, she did not seek medical help until noticing that the mass was gradually enlarged. Both ultrasonography and mammography indicated that the lesion was breast cancer. However, ultrasound-guided core needle biopsy revealed diffuse large B-cell lymphoma of breast and PET-CT scan showed that the lesion was a primary hypermetabolic tumor of left breast. The patient subsequently received comprehensive treatment based on six cycles of rituximab-cyclophosphamide, hydroxydaunomycin, oncovin, prednisone (R-CHOP) chemotherapy. J Med Cases. 2021;12(5):181-185 doi: https://doi.org/10.14740/jmc3660

METABOLIC SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY WITH THE NEW RADIOPHARMACEUTICAL ⁹⁹ᵐTc-1-thio-D-glucose IN THE DIAGNOSIS AND MONITORING OF THE PRIMARY BREAST LYMPHOMA (CASE REPORT)

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study.

METABOLIC SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY WITH THE NEW RADIOPHARMACEUTICAL ⁹⁹ᵐTc-1-thio-D-glucose IN THE DIAGNOSIS AND MONITORING OF THE PRIMARY BREAST LYMPHOMA (CASE REPORT)

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study.

First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial.

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.

A multicentre retrospective study of primary breast diffuse large B-cell and high-grade B-cell lymphoma treatment strategies and survival

ABSTRACT Objectives: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) and primary breast high-grade B-cell lymphoma (PB-HGBCL) are rare extranodal aggressive B-cell lymphomas with distinct characteristics. Reliable data regarding appropriate treatment of these specific entities are lacking due to their rarity. Methods: We reviewed 36 patients diagnosed at four Chinese medical centres between January 2008 and December 2018. Data regarding clinicopathological features, therapeutic evaluation and central nervous system (CNS) relapse were collected, and overall survival (OS) and progression-free survival (PFS) were calculated. Results: Among the 36 patients, there were 29 PB-DLBCL patients and 7 PB-HGBCL patients. The 5-year OS for PB-DLBCL and PB-HGBCL was 75.9% and 28.6%, respectively. The 5-year PFS for PB-DLBCL and PB-HGBCL was 69.0% and 14.3%, respectively. The R-DAEPOCH regimen was significantly more effective in PB-DLBCL patients than the R-CHOP regimen (5-year OS: 78.9% vs 62.5%, P=0.024; 5-year PFS: 73.7% vs 50.0%, P=0.037) but resulted in more severe myelosuppression (P=0.025). The rate of CNS relapse was 17.2% in PB-DLBCL patients and 28.6% in PB-HGBCL patients; the difference was not significant (P=0.602). The R-DAEPOCH regimen did not predominantly reduce CNS recurrence as expected (P=0.616). The Cox proportional hazards model revealed that risk stratification and triple expression were independent prognostic factors. Conclusion: Current treatments, including more intensive chemotherapy regimens, achieve good control of the disease. Novel drugs combined with cellular immunotherapy initially show promising therapeutic effects, and more clinical trials are required to confirm these effects further.

A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL), the most common histologic subtype of lymphoid malignancy in the breast, is a clinically and genetically heterogeneous disease that has insufficient systematic studies on the pathological and molecular features, optimal treatment scheme, as well as the prognostic factors. The aim of our study was to identify biomarkers and distinct subtypes of PB-DLBCLs and then evaluate the prognosis of this rare malignant lymphoma. We carried out hierarchical clustering analysis to evaluate protein expressions of potential biomarkers detected by immunohistochemistry staining of samples from 68 PB-DLBCL patients. The gene expression data from TCGA database was obtained to validate the identified clusters. We identified three robust clusters based on the B-cell receptor (BCR) signaling pathway, including two recognized NF-κB-dependent and PI3K-dependent clusters, and a distinct subset of PB-DLBCL with NF-κB-independent anti-apoptotic overexpression plus PI3K signaling, which exhibited an evolving definition and distinctive characters of a cluster group. Furthermore, survival analysis results showed an inferior outcome in NF-κB-dependent cluster patients and favorable survival in the PI3K-dependent cluster patients, suggesting an important predictive value of the three clusters. Our study provided a new perspective for understanding clinical complexity of PB-DLBCLs, and gave evidence for finding targeted biomarkers and strategies.

Rituximab-CHOP and Central Nervous System Prophylaxis Using Intrathecal Methotrexate in Primary Breast Diffuse Large B-Cell Lymphoma: A Prospective, Multicenter, Single-Arm Phase II Study

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). To prevent CNS recurrence, we designed this phase II trial that addressed feasibility and activity of conventional immunochemotherapy and CNS prophylaxis. Methods: This prospective, multicenter, single-arm phase II study was conducted to evaluate efficacy and safety of 6 cycles of conventional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP) with the addition of 4 doses of intrathecal methotrexate (IT MTX; 12mg) during the first 4 cycles of R-CHOP in patients with primary breast DLBCL. Primary breast lymphoma was defined as lymphoma involving one or both breasts as a sole extranodal site regardless of specific nodal involvement status. The primary end-point was 2-year progression-free survival (PFS). Secondary end-points included cumulative incidence of CNS recurrence, overall survival (OS), and safety. All patients provided written informed consents and the study was registered at www.clinicaltrials.gov as #NCT01448096. Results: Thirty-three patients with primary breast DLBCL were enrolled between Jan 2012 and Jul 2017 in the Consortium for Improving Survival of Lymphoma (CISL) member institutions. The median age was 50 years at diagnosis (range, 29-75) and all were female. Right breast involvement was more common than left (18 [55%] vs 14 [42%]) and bilateral breast involvement was found in one patient (3%). Nodal involvement was present in 16 patients (49%), primarily in regional nodes (14 patients). Thus, the Ann Arbor stage was IE in 17 (52%), IIE in 13 (39%), IIIE in 2 (6.1%), and IV in 1 (3.0%). ECOG performance status was ≥2 in 1 patient (3%) and serum LDH level was elevated in 9 (27%). Therefore, the IPI and the CNS-IPI risk were mainly low (28 patients, 85%; respectively). No patients had CNS involvement at diagnosis. 32 (97%) of the 33 patients completed R-CHOP as planned, and the remaining patient withdraw a consent after four cycles of R-CHOP because of poor tolerance. CNS prophylaxis using IT MTX was completed as planned in 31 patients (94%), but it was discontinued in 2 patients because of patient's refusal. These 2 patients received two and three IT MTX doses, respectively. 32 patients (97%) were evaluable for treatment response and all these patients achieved a complete response. At the cutoff date of this analysis (10 Jul 2019), all patients who entered a follow-up phase had at least 24.0 months of follow-up. With a median follow-up duration of 46.1 months (IQR 31.1-66.8), 6 patients had experienced treatment failure and 3 of these died. The 2-year PFS and OS were 81.3% (95% CI, 67.7-94.8) and 93.5% (95% CI, 84.9-100.0), respectively (fig 1A and B). Of the 6 patients with treatment failure, diseases involved CNS with or without lymph nodes in 4 patients and breasts in 2 patients (1 ipsilateral and 1 contralateral breast recurrence). 3 of the four patients with CNS recurrence had isolated CNS recurrences (2 brain parenchymal and 1 meningeal disease) and one had a concurrent meningeal and lymph nodal recurrence. All 4 patients with CNS recurrence had received prophylactic IT MTX as planned by protocol. The 2-year cumulative incidence of CNS recurrence, taking into account the competing risk of death, was 12.5% (95% CI, 0.3-23.2, fig 1C). Although the number of patients with intermediate CNS-IPI risk was small (5 patients, 15%), the cumulative incidence of CNS recurrence did not differ significantly according to the CNS-IPI risk group. All CNS recurrences occurred within the first 2 years after enrolment. Toxicities were generally manageable during the R-CHOP and IT MTX treatment. No deaths as a result of toxicity occurred during treatment. Conclusion: Our study shows that conventional R-CHOP with prophylactic IT MTX is feasible in patients with primary breast DLBCL. However, given a substantially high rate of CNS recurrence, further studies to properly define the best strategy for CNS prophylaxis should be needed in patients with primary breast DLBCL. Figure 1 Disclosures Yoon: F. Hoffmann-La Roche Ltd: Research Funding. Kim:Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Prognosis analysis of primary breast diffuse large B cell lymphoma

Objective: To investigate the clinical characteristics, therapy modality and prognosis of primary breast diffuse large B-cell lymphoma(PB-DLBCL). Methods: A total of 68 patients with PB-DLBCL treated in Tianjin Medical University Cancer Institute and Hospital were enrolled between January 1, 2004 and January 31, 2017. Clinicopathological data were retrospectively analyzed. 67 patients were female and only one male. The median age was 56 years old. 46 patients had Ann Arbor clinical stageⅠ~Ⅱ disease, and the other 22 were stage Ⅲ~Ⅳ. The patients with and without B symptom were 11 and 57, respectively. Kaplan-Meier method was used for univariate analysis to calculate the 5-year overall survival (OS) rate and 5-year progress-free survival (PFS) rate, compared using the log rank test. Cox regression analysis was used for multivariate analysis. Results: The 1, 3, 5-year OS rate were 84.0%, 78.0% and 73.0%, and 1, 3, 5-year PFS rate were 80.0%, 71.0% and 51.0%, respectively. Univariate analysis indicated that eastern cooperative oncology group (ECOG) score, Ann Arbor clinical stage, international prognostic index (IPI) score, risk stratification, B symptom, β2-microglobulin(β2-MG) level, size of the tumor and cycles of chemotherapy were prognostic factors for OS (all P<0.05), and Ann Arbor clinical stage, IPI score, risk stratification and B symptom were prognostic factors for PFS (all P<0.05). Multivariate analysis indicated that Ann Arbor clinical stage was independent prognostic factor for OS(P=0.029) and B symptom was independent prognostic factor for PFS(P=0.028). Conclusions: Prognosis of PB-DLBCL was relatively good. Ann Arbor clinical stage and B symptom were independent prognostic factors for OS and PFS, respectively.

Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB‐DLBCL patients. We retrospectively reviewed data on 108 PB‐DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow‐up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5‐year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5‐year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10‐year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB‐DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB‐DLBCL patients.

1034P - A prospective multicenter study of primary breast lymphoma in the rituximab era: Prognostic implication of beta 2 microglobulin and interlukin-6 & interlukin-10

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity representing ≤ 2% of extra-nodal non-Hodgkin lymphoma. We aimed to define clinical profile, prognostic factors and the incidence of the central nervous system (CNS) relapse in the era of rituximab and clarify the prognostic value of beta2 microglobulin(B2M), interlukins-6 (IL-6) and interlukin -10(IL-10). Methods: Between Jan 2012 to Dec 2016, a prospective analysis of 28 patients presenting to 7 academic Egyptian centers. All patients were females. Only patients with newly diagnosed stage I and II disease DLBCL were included. Patients with evidence of baseline CNS disease and patients with hepatitis B and HIV were excluded. All patients were scheduled to receive R-CHOP protocol plus involved- field radiotherapy. The prognostic significance of B2M, and IL-6 and 10 were assessed. Results: About 75% presented with breast mass, 4 cases with inflammatory symptoms, 3 cases were discovered by mammography. Right breast was more involved (64%), 86% had ≤ 1 ECOG performance status, and LDH elevated was in 39% and 18% had B symptoms. HCV was positive in 32% (9 patients). Stage I was detected in 57%. The stage–modified International prognostic index was ≤1 in 54%. Ten cases underwent breast surgery (2 modified radical mastectomy, 8 conservative breast surgery). Complete response was achieved in 23/28 (82%) with median follow-up of 28 months, 39% of patients had relapsed, contralateral breast was the site of initial relapse in two cases, 11% developed CNS relapse and 21% in other nodal and extranodal sites. Three years disease free survival and overall survival were 68% and 79%. Favorable prognostic factors according to univariate analysis were stage I, IPI≤1, tumor size < 5cm, B2M. IL6 and IL-10, while for multivariate analysis they were IPI≤1 and B2 M and IL-6. Conclusions: Primary breast DLBCL has high rate of CNS relapse in spite of era of rituximab so CT or MRI of CNS is necessary during follow-up. Prophylaxis to CNS should be considered in the initial treatment to improve outcome. In addition, assessment of pretreatment serum levels of B2M, and IL-6 in newly diagnosed DLBCL may indicate a possible prognostic role. Legal entity responsible for the study: Lobna Ezz el-arab. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.