Breast Lymphoma Research Articles

Bioconjugates: A New Class of Therapeutics for Cancer Treatment

Bioconjugates represent a novel class of therapeutics that offer promise in the treatment of cancer. These compounds are formed by combining a targeting molecule, such as an antibody or peptide, with a therapeutic agent, such as a chemotherapy drug or toxin. This approach allows for targeted delivery of the therapeutic agent to cancer cells, minimizing damage to healthy tissues and reducing side effects. Bioconjugates have shown significant potential in preclinical and clinical studies, with several FDA-approved drugs currently available for the treatment of cancer.
 There are several types of bioconjugates currently being developed for cancer treatment, including antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and nanoparticle-drug conjugates (NDCs). ADCs are the most well-established type of bioconjugate and have been approved for the treatment of several types of cancer, including breast cancer, lymphoma, and leukemia. PDCs and NDCs are newer classes of bioconjugates that are still in the preclinical and early clinical stages of development. Ongoing research in this field aims to improve the efficacy and safety of bioconjugates and expand their use to a wider range of cancer types. As research in this field continues to advance, we can expect to see even more innovative and effective bioconjugate drugs being developed in the future. These drugs are designed to target specific cancer cells, while leaving healthy cells unharmed, and have the potential to revolutionize cancer treatment. Furthermore, bioconjugates can be tailored to individual patients, allowing for personalized and targeted cancer therapy.

Primary breast lymphoma: a case series and review of the literature

BackgroundPrimary breast lymphoma (PBL) is a very rare form of non-Hodgkin's lymphoma (NHL), defined as a malignant primary lymphoma occurring in the breast in the absence of previously detected lymphoma localizations. Our study aims to retrospectively evaluate the epidemiological, clinical, and imaging findings and therapeutic features of breast lymphomas in patients with primary lymphoma of the breast.Materials and methodsThis is a retrospective study including 13 patients with primary non-Hodgkin's lymphoma of the breast treated at the Salah Azaiez Institute of Oncology from 2000 to 2019. This sample includes 1 case of follicular lymphoma, 2 cases of large T-cell lymphoma, and 10 cases of large B-cell lymphoma.ResultsPatients included in the study were aged between 17 and 89 years (average age of 52.6 years). All patients were referred because of a lump in the breast, and only one patient consulted with inflammatory signs in the breast. The average clinical size of the tumor was 7.2 cm, with a maximum of 15 cm. Mammography showed an oval mass with circumscribed margins in the majority of cases. Ultrasound showed in most cases a hypoechoic irregular mass or multilobulated mass with irregular margins and hypervascular on color Doppler. Magnetic resonance imaging (MRI) was performed on only three patients and showed a spiculated lesion with polycyclic limits. Eight patients underwent surgery. In our study breast lymphomas involved 10 cases of large B-cell lymphoma, one case of follicular lymphoma, and two cases of large T-cell lymphoma. In this series, 11 patients had localized stages (I + II) at diagnosis, and 2 patients had disseminated stages (stage III) of primary breast lymphoma. Seven patients underwent chemotherapy treatment alone, and five had chemotherapy with radiotherapy. The median follow-up of our patients was 53 months, ranging from 1 to 177 months. Overall survival was 71% at 3 years and 51% at 5 years.ConclusionPrimary breast lymphoma is an uncommon type of breast malignancy. The optimal treatment modality is still in question because of the rarity of this disease. However, the use of combination therapy produces the most favorable results. Surgery is not yet recommended.

A Review on the Neurotoxic Effects of Doxorubicin.

Anthracyclines, a class of drugs considered as most effective anticancer drugs, used in the various regimens of cancer chemotherapy, induce long-term impairment of mitochondrial respiration, increase reactive oxygen species, and induce other mechanisms potentially leading to neurotoxicity. According to literature findings, one drug of this class - doxorubicin used to treat e.g. breast cancer, bladder cancer, lymphoma, and acute lymphocytic leukemia may induce such effects in the nervous system. Doxorubicin has poor penetration into the brain due to the lack of drug penetration through the blood-brain barrier, thus the toxicity of this agent is the result of its peripheral action. This action is manifested by cognitive impairment and anatomical changes in the brain and peripheral nervous system found in both preclinical and clinical studies in adult patients. Furthermore, more than 50% of children with cancer are treated with anthracyclines including doxorubicin, which may affect their nervous system, and lead to lifelong damage in many areas of their life. Despite ongoing research into the side effects of this drug, the mechanism of its neurotoxicity action on the central and peripheral nervous system is still not well understood. This review aims to summarize the neurotoxic effects of doxorubicin in preclinical (in vitro and in vivo) research and in clinical studies. Furthermore, it discusses the possible mechanisms of the toxic action of this agent on the nervous system.

P-415 Cryostorage of human ovarian tissue: Evaluating the storage and disposal pattern of a 22-year period with 2475 patients

Abstract Study question What are the characteristics of patients who did ovarian tissue cryopreservation? Summary answer Patients store their ovarian tissue in average 5 years, when storage is actively ended about 50% of the patients conceived without using the frozen tissue. What is known already In female fertility protection two major options for cryopreservation are available today: cryopreservation of oocytes and ovarian tissue cryopreservation (OTC). If cryopreservation of oocytes is not feasible, OTC remains the only option for individual fertility protection in women, adolescents and especially prepubertal girls. Study design, size, duration The relevant parameters of a single university center were revised and digitalized in the period from 2019 to 2021 and were analyzed in the time period between 2000 and 2021. Participants/materials, setting, methods 2475 patients with stored ovarian tissue were analyzed. Data extraction was done with MedITEX (CRITEX) and processed with SPSS (IBM). To assess the patient motivation of storage, patients were contacted by letter, e-mail and telephone calls. Main results and the role of chance On average, patients were aged 26.8 years, diagnosed with breast cancer (44.8%) and lymphoma (22.4%) in majority. In the active storage group (n = 1320) patients were storing for 5.4 years, patient age was 25 years at time of OTC and indications were breast cancer (37.6%) and lymphoma (26.7%). Analyzing the longtime storage group ≥10 years (n = 148), patient age was 23.8 years at time of OTC, storage duration was 12 years and indications were again mainly breast cancer (27%) and lymphoma (27.7%). When patients deceased (n = 133), patient age was 28.1 years, with a storage duration of 2.7 years and initially diagnosed with breast cancer (39.8%) and sarcoma (17.3%). When storage ended (n = 1155), patients stored for 4.2 years, mean age was 33 years. Analyzing the mode of storage end we observed that 2.5% had a transplantation on site, 10.3% transferred their tissue to another cryobank while 11.5% deceased. The majority of this group (75.7%) ended their storage due to pregnancy (49.1%), no desire to have children (25.9%), too expensive storage fees (8.9%), death (8.5%), recurrence of cancer (8.5%), no partner (4%) and fear of surgery in the future (3.1%). 6.7% regretted the end of storage retrospectively. Limitations, reasons for caution Live birth rate was not part of this paper as our main intention was to explore the storage characteristics. Few patients transferred a part of the samples for retransplantation while still storing tissue on site. The response rate of 28.8% limits the scope for interpretation regarding end of storage. Wider implications of the findings The pregnancy rate resulting from ovarian tissue that wasn't removed for OTC (49,1%) supports the approach of removing only 50% of one ovary. The long storage time and the fact that 6.7% regretted the end of storage, shows how important the OTC is, it should be covered by health insurances. Trial registration number not applicable

Epidemiology and a Predictive Model of Prognosis Index Based on Machine Learning in Primary Breast Lymphoma: Population-Based Study.

Primary breast lymphoma (PBL) is a rare disease whose epidemiological features, treatment principles, and factors used for the patients' prognosis remain controversial. The aim of this study was to explore the epidemiology of PBL and to develop a better model based on machine learning to predict the prognosis for patients with primary breast lymphoma. The annual incidence of PBL was extracted from the surveillance, epidemiology, and end results database between 1975 and 2019 to examine disease occurrence trends using Joinpoint software (version 4.9; National Cancer Institute). We enrolled data from 1251 female patients with primary breast lymphoma from the surveillance, epidemiology, and end results database for survival analysis. Univariable and multivariable analyses were performed to explore independent prognostic factors for overall survival and disease-specific survival of patients with primary breast lymphoma. Eight machine learning algorithms were developed to predict the 5-year survival of patients with primary breast lymphoma. The overall incidence of PBL increased drastically between 1975 and 2004, followed by a significant downward trend in incidence around 2004, with an average annual percent change (AAPC) of -0.8 (95% CI -1.1 to -0.6). Disparities in trends of PBL exist by age and race. The AAPC of the 65 years or older cohort was about 1.2 higher than that for the younger than 65 years cohort. The AAPC of White patients is 0.9 (95% CI 0.0-1.8), while that of Black patients was significantly higher at 2.1 (95% CI -2.5 to 6.9). We also identified that the risk of death from PBL is multifactorial and includes patient factors and treatment factors. Survival analysis revealed that the patients diagnosed between 2007 and 2015 had a significant risk reduction of mortality compared to those diagnosed between 1983 and 1990. The gradient booster model outperforms other models, with 0.752 for sensitivity and 0.817 for area under the curve. The important features established with the gradient booster model were the year of diagnosis, age, histologic type, and primary site, which were the 4 most relevant variables to explain 5-year survival status. The incidence of PBL started demonstrating a tendency to decrease after 2004, which varied by age and race. In recent years, the prognosis of patients with primary breast lymphoma has been remarkably improved. The gradient booster model had a promising performance. This model can help clinicians identify the early prognosis of patients with primary breast lymphoma and therefore improve the clinical outcome by changing management strategies and patient health care.

Clinical utility of a novel non-invasive technology for monitoring severe neutropenia in anticancer therapy.

e13632 Background: Every year more than 140,000 patients receiving anticancer therapy for malignancies in the US experience febrile neutropenia. Early detection of severe neutropenia could enable preventive strategies to reduce the incidence of febrile episodes. PointCheck is a novel portable optical device that can noninvasively monitor for severe neutropenia at home using microscopy and artificial intelligence. Preliminary clinical results of this device including usability (Lamaj et al., 2022), and sensitivity, and specificity (Pablo-Trinidad et al., 2019) for detection of severe neutropenia have already been reported. Here, we describe an exploratory clinical utility subanalysis. Methods: We conducted an international multicenter study with a primary endpoint of usability including mainly patients with hematological or breast cancer receiving therapy with intermediate/high risk for severe neutropenia, tested at two time points (baseline and nadir tests). Data included demographic information, cancer type, and a differential cell count within 120 minutes of the optical testing. The treating physician also completed an exploratory survey with 11 questions about the device´s potential clinical utility. A mixed-methods approach (descriptive statistics & “Likert” analyses with R 4.2.2) was used to evaluate the results. Results: 79 patients were included in this exploratory subanalysis. The median age was 49.5 (IQR 10.5-78.5) years, and 64 (81%) patients were female. The most common diagnoses were breast cancer (63%) and lymphoma (20%). Preliminary utility results were favorable with attending physicians agreeing that PointCheck could have helped evaluate 85% of the patients. In 82% of the patients, physicians felt that the device could avoid preparation of chemotherapy infusions in the setting of neutropenia. In 73% of the patients, physicians would consider administration of G-CSF or prophylactic antibiotics when sustained grade IV neutropenia was detected. Conclusions: This novel technology is able to non-invasively monitor for severe neutropenia and can add clinical utility as assessed by treating oncologists. Further studies are needed to validate these results.

Impact of the oncology care model (OCM) on Medicare payments, utilization, and care delivery: Update through year 5.

1512 Background: OCM was a voluntary episode-based alternative payment model designed to improve the value of care for fee-for-service Medicare beneficiaries receiving systemic therapy for cancer. Participating practices received monthly enhanced oncology services (MEOS) care coordination payments and could receive additional payments (or penalties) if they met quality and total episode spending goals during 6-month episodes. Methods: We used a difference-in-differences approach to evaluate OCM impacts on Medicare payments, utilization, and quality measures during 6-month episodes before (July ‘14-January ’16) and after (July ‘16-June ‘21) OCM’s start. Patient-episodes were attributed to OCM-participating practices (n = 202) or propensity-matched comparison practices (n = 534). Statistical significance was defined as p≤0.10 to avoid missing program impacts. Results: Total episode payments (TEP) for 6-month OCM episodes increased from 29,120 in the baseline period to 35,467 in the OCM period (+21.8%). In reference to comparison episodes, OCM led to a 499 relative reduction in TEP (90%CI -771, -227, -1.7% relative to baseline.) OCM had no significant impact on TEP for low-risk breast, prostate, and bladder cancers, and OCM led to a relative decrease of 755 (CI -1140, -371) for all other higher risk cancers. Reductions in TEP were largest for high-risk breast cancer, lymphoma, lung cancer and colorectal cancer. The overall OCM impact on TEP was attributable to relative reductions in both Part A payments (-152, [CI -257, -47]) and Part B payments (-276, [CI -459, -92]). There was no OCM impact on Part D payments. While OCM had no impact on Part B chemotherapy payments, OCM reduced Part B non-chemotherapy drug payments by 251 (CI -330, -173; -9.3%). Utilization analyses showed no impact of OCM on ED visits or hospitalizations, but OCM reduced the likelihood of ICU admission by 0.6 percentage points (PP; CI -1.0, -0.1, -5.4%). OCM had no impact on initial chemotherapy regimen selection, but OCM led to greater use of biosimilar cancer therapies and value sensitive changes in the use of antiemetics, bone supportive medications, and WBC growth factors (including greater use of biosimilar WBC growth factors; all p < 0.10). OCM reduced hospitalizations in the last 30 days of life by 0.8 PP (CI -1.6, -0.1; -1.5%) with no impact on use of chemotherapy or hospice at the end of life. Despite OCM-related TEP reductions, OCM resulted in net losses to Medicare after accounting for MEOS and performance-based payments. Conclusions: OCM led to reductions in TEP with similar or improved quality. Reductions in TEP were greatest for common, high-cost cancer types and were driven primarily by changes in use of supportive care medications. The Medicare Enhancing Oncology Model will build on the experience of OCM to further the goal of improving the quality and value of cancer care for Medicare beneficiaries.

Landscape and Regulatory Perspective on Oncology Drugs in Pregnancy

AbstractCancers affecting pregnant women include breast cancer, melanoma, thyroid cancer, cervical cancer, lymphomas, and leukemias. The medical management of cancer during pregnancy with molecularly targeted oncology drugs remains quite challenging, with knowledge gaps about the drugs’ safety and efficacy due to exclusion of pregnant women from cancer clinical trials, discontinuation of individuals who become pregnant during clinical trials, and limited information on appropriate dosing of molecularly targeted oncology drugs during pregnancy. Physiological changes occur during pregnancy and may result in alterations in the absorption, distribution, metabolism, and excretion of drugs used in pregnant women. Physiologically based pharmacokinetic modeling that incorporates physiological changes induced by both the cancer disease state and pregnancy has the potential to inform dosing of molecularly targeted oncology drugs for pregnant women, improve our understanding of the pharmacokinetic changes associated with pregnancy in patients with cancer, facilitate the design of potential studies of molecularly targeted oncology drugs in pregnant women to support dosing recommendations, and provide model‐informed pharmacokinetic data to support regulatory decision making.

Sonographic Features of Primary Breast Lymphoma: An Analysis of 10 Cases.

Primary breast lymphoma (PBL) is a rare malignant breast tumor. The literature concerning PBL ultrasound is based primarily on case reports, with only a few cases reported to date. This study aimed to elucidate the sonographic characteristics of PBL and explore the value of ultrasonography in the preoperative diagnosis of PBL using the Breast Imaging Reporting and Data System (BI-RADS). A retrospective review of files involving a diagnosis of PBL (2013-2020) was conducted in the Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, and the First Affiliated Hospital of Wenzhou Medical University, Wenzhou. The clinical characteristics and sonographic features of 12 lesions in 10 patients were analyzed and discussed in light of the literature. All patients, aged 50.40 ± 14.31 years (range 30-66 years), had clinically palpable lumps. Most cases were on the right breast and were unilateral. Only one patient had mucosa-associated lymphoma. The histological type of the other patients was diffuse large B-cell lymphoma (DLBCL). Ultrasonography revealed nodular and diffuse PBL lesions without internal calcification. The nodular PBL was hypoechoic or mixed hypo- to hyperechoic, with a differential lobulated shape and horizontal growth. Although color Doppler flow imaging (CDFI) showed no significant features, the ultrasound findings were categorized as BI-RADS 4 in 10 of the 12 lesions and BI-RADS 5 in two lesions. All patients were suspected of having malignancies (BI-RADS 4 or 5). PBL was mostly found in middle-aged and elderly women, and the right breast was more prone to the development of malignancies. PBL lesions were classified as either nodular or diffuse based on the boundaries of the tumors in the ultrasound images. Typical PBL was characterized by hypoechoic or heterogeneous lesions with circumscribed or microlobulated margins and horizontal growth. The sonographic features of the PBL lesions and the BI-RADS categorizations of the lesions analyzed suggested malignancy.

Cryostorage of human ovarian tissue: evaluating the storage and disposal pattern over a 22-year period in 2475 patients

Research questionWhat are the parameters of age, indications for ovarian tissue cryopreservation, storage characteristics and reasons for tissue disposal in a large cohort of individuals undertaking cryopreservation? DesignThe relevant parameters in a single university centre were revised and digitalized in the period from 2019 to 2021. To assess patients’ motivation at the end of storage, patients were contacted by letter, e-mails and telephone calls. ResultsA group of 2475 patients with stored ovarian tissue were analysed in the time period between 2000 and 2021; the response rate for contact calls and letters was 28.8% (224/777). Where storage had ended (n = 1155), patients had on average stored for 3.8 years and begun storing at age 30 years; the main indications were breast cancer (53%) and lymphoma (17.5%). Of these participants, 2.5% had a transplantation on site, 10.3% transferred their tissue to another cryobank and 11.5% were deceased. The majority of the group (75.7%) ended their storage due to pregnancy (49.1%), a lack of desire to have children (25.9%), storage fees that were too expensive (8.9%), death (8.5%), recurrence of cancer (8.5%), lack of a partner (4%) and fear of surgery in the future (3.1%); 6.7% retrospectively regretted ending storage. ConclusionsThe pregnancy rate of 49.1%, resulting from ovarian tissue that was not removed during surgery for scheduled ovarian tissue cryopreservation supports the clinical approach of removing and cryopreserving only 25–50% of one ovary. It is proposed that interdisciplinary counselling should be implemented not only prior to fertility preservation, but also when intending to end storage.

Locally advanced primary breast lymphoma: a rare case report

BackgroundPrimary Breast Lymphoma is a rare manifestation of extranodal non-Hodgkin lymphoma and accounts for less than 1% of all breast malignancies. It is defined by localized involvement of the mammary tissue by lymphomatous infiltrate in the absence of prior extramammary lymphoma and concomitant widespread disease.Case presentationA 46-year-old melanodermic woman was referred to our hospital due to an extensive ulcerated right breast lesion with signs of infection. Imaging studies revealed a large breast tumor invading the chest wall, with cortical disruption of adjacent ribs and associated pleural thickening. Later, it was complicated with a bronchopleural cutaneous fistula. Biopsy of the mass was performed and the histopathologic diagnosis was consistent with breast infiltration by diffuse large B-cell lymphoma. Concurrent widespread lymphomatous disease and preceding extramammary lymphoma were excluded. Firstly, antibiotic therapy was instituted and surgical debridement was performed in order to control the infection. Afterwards, she underwent chemotherapy and local radiotherapy, with radiologic complete response.ConclusionsThe diagnosis of primary breast lymphoma is challenging because this disease has non-specific symptoms and imaging features. Radio–pathological correlation and exclusion of systemic lymphoma are essential to establish the diagnosis and to minimize potential complications.

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients.

There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care. De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals. Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

Primary extranodal lymphomas: Five-year experience from a tertiary care center of North India.

Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type-48%, nongerminal center-52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes.

A Physiologically Based Pharmacokinetic Model to Predict Determinants of Variability in Epirubicin Exposure and Tissue Distribution.

Epirubicin is an anthracycline antineoplastic drug that is primarily used in combination therapies for the treatment of breast, gastric, lung and ovarian cancers and lymphomas. Epirubicin is administered intravenously (IV) over 3 to 5 min once every 21 days with dosing based on body surface area (BSA; mg/m2). Despite accounting for BSA, marked inter-subject variability in circulating epirubicin plasma concentration has been reported. In vitro experiments were conducted to determine the kinetics of epirubicin glucuronidation by human liver microsomes in the presence and absence of validated UGT2B7 inhibitors. A full physiologically based pharmacokinetic model was built and validated using Simcyp® (version 19.1, Certara, Princeton, NJ, USA). The model was used to simulate epirubicin exposure in 2000 Sim-Cancer subjects over 158 h following a single intravenous dose of epirubicin. A multivariable linear regression model was built using simulated demographic and enzyme abundance data to determine the key drivers of variability in systemic epirubicin exposure. Multivariable linear regression modelling demonstrated that variability in simulated systemic epirubicin exposure following intravenous injection was primarily driven by differences in hepatic and renal UGT2B7 expression, plasma albumin concentration, age, BSA, GFR, haematocrit and sex. By accounting for these factors, it was possible to explain 87% of the variability in epirubicin in a simulated cohort of 2000 oncology patients. The present study describes the development and evaluation of a full-body PBPK model to assess systemic and individual organ exposure to epirubicin. Variability in epirubicin exposure was primarily driven by hepatic and renal UGT2B7 expression, plasma albumin concentration, age, BSA, GFR, haematocrit and sex.

Clinicopathological characteristics, local treatment, and prognostic factors in IE/IIE primary breast lymphoma: a retrospective study of 67 patients

IntroductionPrimary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods.Materials and methodsRecords of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher’s exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis.ResultsAt the median follow-up time of 65.23 months (range, 9–150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p < 0.001) were statistically associated with longer PFS in patients with PBL. Nodal sites involved and radiotherapy administration were significant predictors for 5-year OS. Multivariate analysis suggested that nodal sites involved (p = 0.005) and radiotherapy administration (p < 0.003) were independent prognostic factors for OS in patients with PBL (p < 0.05). Radical surgery was not an independent factor for patients with PBL.ConclusionsRadiotherapy improved the survival of patients with PBL. Radical mastectomy offered no additional benefit in the treatment of PBL.

Abstract 4771: Prevention of doxorubicin-induced cardiotoxicity by benfotiamine

Abstract Anthracyclines such as daunorubicin and doxorubicin (DOX) are currently used as chemotherapeutic agents in the prevention of various cancers including breast cancer, lung cancer, leukemia, and lymphoma. Although, anthracyclines are successful in controlling various cancers growth, the major drawback is the unwanted cardiotoxicity. Specifically, high doses of DOX used for the therapy of advanced cancers could cause life threating conditions. Therefore, specific interventions are required to decrease the cardiac toxicity associated with the DOX. Benfotiamine, a lipid soluble vitamin B1 derivative has shown be a potent anti-oxidant and anti-inflammatory agent. However, the efficacy of benfotiamine in the prevention of cardiotoxicity associated with the anthracyclines is not known. In this study, we examined the effect of benfotiamine in the prevention of DOX-induced cytotoxicity in the human umbilical vascular endothelial cells (HUVECs). Treatment of HUVECs with DOX caused significant endothelial cells death and benfotiamine in a concentration-dependent manner prevented the dox-induced endothelial cell death. Further, benfotiamine prevents the DOX-induced apoptosis in endothelial cells by preventing the activation of caspase-3. Benfotiamine also prevents DOX-induced reactive oxygen species generation. Our results also indicate that benfotiamine regulates DOX-induced expression of pro-apoptotic mediators such as BAD, phosphor-P53, and pro-caspase-3, and anti-apoptotic mediators such as BCL-2, BCL-x, IAPs, and HSP and others such as FADD, DR5, and SMAC/diablo. We plan to further explore how benfotiamine prevents DOX-induced cardiotoxicity using human cardiac myocytes and mouse models. Thus, based on our cell culture studies, benfotiamine through its potent anti-oxidative property could prevent endothelial cytotoxicity and suggests that it could be further developed as adjuvant therapy in controlling cardiotoxicity associated with the anthracycline chemotherapy. Citation Format: Justin R. Taylor, Kyra Harames. Prevention of doxorubicin-induced cardiotoxicity by benfotiamine. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4771.

Abstract 1459: Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B

Abstract c-MYC is a master transcription factor overexpressed in more than 70% of human cancers including breast cancers (TNBC), lung cancers, brain tumors, prostate cancers, lymphomas, pediatrics cancers, pancreatic cancers, colorectal cancers, and ovarian cancers. Yet there is no clinically approved drug that directly targets it. The lack of direct clinically approved inhibitors of c-MYC is a significant biological and clinical question that needs urgent attention, especially in the context of aggressive cancers such as MYC driven triple negative breast cancer. In the USA, TNBC accounts for 10.34% of breast cancers, in China the rate is at 14%, and in African Americans the rate is 40%. We engineered the stable polyU sequences on the 3’UTR of c-MYC into unstable forms and specifically destabilized and degraded c-MYC transcript and protein and controlled primary tumor and metastasis in vivo. We developed three c-MYC destabilizing constructs that were effective in TNBC. They specifically destabilized c-MYC transcript, degraded c-MYC protein and the transcription factors STAT5A/B with increased expression of active caspase 3/7 leading to cancer cell death. In vivo, we delivered nanocage complexed with the MYC destabilizing constructs into TNBC mice bearing tumor and achieved reduction of primary tumor volume by 60-80%, 80% reduction in secondary tumor metastasis and very significant survival outcome (p&amp;lt;0.0001). Mechanistically, the destabilization of c-MYC degraded c-MYC and its super enhancer interacting partner, STAT5A/B, in primary tumors and metastatic tumors. Taken together, we have developed a novel therapy for TNBC and uncovered c-MYC super enhancer STAT5A/B interaction as the target Citation Format: Chidiebere U. Awah, Joo Sun Mun, Baris Boylu, Alooka Paragodaarachchi, Chika Ochu, Junfei Zhang, Hiroshi Mastui, Olorunseun Ogunwobi. Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1459.

BREAST LYMPHOMA

Primary breast lymphoma is a very rare histological entity of breast cancer. The Clinical and radiological aspects do not present any particular specificities. Diagnosis is often delayed. The treatment is mainly based on chemotherapy. We report the case of a patient with high grade malignant non-Hodgkin lymphoma. The symptomatology was made of breast swelling. The remote extension assessment was negative. The patient received 6 courses of type R mini CHOP chemotherapy followed by three-dimensional radiotherapy with a dose of 30 Gy in 15 fractions for 3 weeks. An echo mammography in between treatment showed: a partial response at 50%. Controle PET CT scan performed 3 weeks after the last cure having objectified: Complete disappearance of the active subcutaneous nodule at the level of the QSE of the right breast. Breast localisation of lymphoma is very rare. His prognosis was considerably improved due to a multidisciplinary approach.

Epidemiological Characteristics of Cancer Patients Attending at Felege Hiwot Referral Hospital, Northwest Ethiopia

Cancer has become a public health problem and a challenge in developing countries, including Ethiopia. There is scanty local data on cancer epidemiology in Amhara region, Ethiopia. Thus, this study aimed to describe epidemiological characteristics of cancer patients attending Felege Hiwot Referral Hospital. This study was based on a patient cancer registry that took place in Bahir Dar Felege Hiwot Referral Hospital, Amhara Regional State, Ethiopia. It is the main referral hospital in the Amhara region, and serves more than 5 million people. The hospital has units including oncology for follow-up health care services. All confirmed cancer patients attending oncology units from July 2017 to June 2019 were included in the study. Global Moran's I statistic was employed to assess spatial heterogeneity of cancer cases across districts. Getis-Ord Gi* statistics was performed to identify hot spot districts with high numbers of cancer cases. In a two-year period, a total of 1888 confirmed cancer patients were registered. There was a significant variation of cancer patients between females (60.8% 95%CI 58.5 to 63.0%) and males (39.3% 95%CI 37.0 to 41.5%). The first three most frequent cancer types seen were breast (19.4%) and cervical cancer (12.9%), and lymphoma (15.7%). Breast and cervical cancer and lymphoma were the first three cancers type among women, whereas lymphoma, sarcoma, and lung cancer were the three most common cancer among men. Spatially, cancer cases were non-random in the study area (global Moran's I = 0.25, z-score = 5.6, p-value < 0.001). Bahir Dar city administration (z = 3.93, p < 0.001), Mecha (z = 3.49, p < 0.001), Adet (z = 3.25, p < 0.01), Achefer (z = 3.29, p < 0.001), Dangila (z = 3.32, p < 0.001), Fogera (z = 2.19, p < 0.05), and Dera (z = 2.97, p < 0.01) were spatially clustered as hotspot with high numbers of cluster cases. We found that there is a variation in the cancer types with sex. This study provides an insight for further exploration of environmental and occupational exposure related factors for cancer to guide future cancer prevention and control programs. The current study also calls for expansion of cancer registry sites, including in rural areas in the region.

Evolution in the Presence and Evidence Category of Radiation Therapy Treatment Recommendations in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology

The changes in the recommended use of radiation therapy (RT) in the presence of expanding systemic cancer therapies and technological advances are poorly characterized. We sought to understand the recommended utilization of RT across a broad range of malignancies by examining National Comprehensive Cancer Network (NCCN) Guidelines. We conducted a comprehensive review and categorization of RT recommendations, with their subsequent supporting evidence categories, in 3 versions of NCCN Guidelines, specifically years 2000, 2009, and 2019. These NCCN Guidelines were individually examined for RT-specific recommendations among the 10 most common tumors. The presence of RT as a recommended modality was recorded for each tumor type in each guideline. Recommendation categories including Category 1, 2A, 2B, and 3 were tallied and compared with examine totals and percentage distributions in each tumor type. A total of 3858 NCCN recommendations were individually reviewed. The presence of a recommendation inclusive of RT increased from incidence of 205 in the year 2000 to 992 in the year 2019 (383%). In the 2019 NCCN Guidelines, the most Category 1 RT recommendations were found within small cell lung (13%), non-small cell lung (5%), breast (5%), bladder (2%), rectal (2%), and non-Hodgkin lymphoma (1%). Pancreatic, uterine, prostate, melanoma, kidney, and colon cancer guidelines had no Category 1 RT recommendations. Rectal cancer had 31 (27%) preferred recommendations. The majority (89%) of 2019 RT recommendations were for initial therapy, and 9% were specific to salvage therapy. Tumor sites with the highest proportion of RT Category 1 evidence were small cell lung (29%), non-small cell lung (24%), and breast cancer (24%). The frequency of recommendations for using RT in NCCN Guidelines has increased by >300% in the past 20 years among the 10 most common malignancies. Consideration of the quality of evidence supporting these recommendations by tumor type is useful to identify specific malignancies in need of higher-level evidence supporting the role of RT.