Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.

PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry. METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle. RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls. CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.

Multidisciplinary Tumor Boards in Dermatologic Surgery.

BACKGROUND: Recent advances in diagnostic and therapeutic modalities have made oncologic care ever more challenging, and multidisciplinary tumor boards (MTBs) are increasingly being used as a forum to discuss and coordinate care for complex oncology patients. Literature on the use of MTBs specific to cutaneous oncology and dermatologic surgery remains limited. OBJECTIVE: To share our experiences with cutaneous oncology MTBs at the University of Vermont Medical Center (UVMMC). METHODS: We describe the formation, timing, participation, clinical discussion, case follow-up, and coordination of care of our MTBs. RESULTS: A log of all cases discussed at cutaneous oncology MTBs from August 2018 to August 2019 is presented as an example. Five specific cases are described in further detail to demonstrate critical components of multidisciplinary care. CONCLUSION: The MTBs at UVMMC has created a collaborative environment for providers in multiple specialties to jointly formulate and coordinate optimal treatment plans for difficult cases, particularly when treatment guidelines do not exist or are insufficient. Furthermore, MTBs can serve as an educational forum for all participants.

The impact of patient age on breast cancer risk prediction models.

BACKGROUND: The impact of age on breast cancer risk model calculations at the population level has not been well documented. METHODS: Retrospective analysis of formal breast cancer risk assessment in 36 542 females ages 40-84 at a single institution from 02/2007 to 12/2009. Five-year and lifetime breast cancer risks were calculated using Gail, Tyrer-Cuzick version 6 (TC6), Tyrer-Cuzick version 7 (TC7), BRCAPRO, and Claus models. Risk of BRCA mutation was calculated using BRCAPRO, TC6, TC7, and Myriad. Eligibility for BRCA testing was assessed using NCCN guidelines. Descriptive analyses were performed and trends in risk were assessed by age. RESULTS: The lifetime risk of breast cancer trended down with increasing age in all risk models. TC7 calculated the highest estimates for lifetime risk for all age ranges and had the highest proportion of patients with a calculated lifetime risk >20%. Five-year risk increased with age in all models. By age 60-64, every risk model predicted a mean 5-year risk ≥1.7%. Myriad estimated >5% risk of BRCA mutation more often than other models for all ages. Risk of BRCA mutation stayed constant with age with Myriad, but trended down with increasing age with TC6, TC7, and BRCAPRO. CONCLUSIONS: More patients have an estimated lifetime risk of breast cancer >20% and qualify for MRI screening with the Tyrer-Cuzick model. All models predict an increased 5-year risk with age, which could impact chemoprevention recommendations. To maximize access to genetic testing, the Myriad model and NCCN guidelines should be used.

Breast cancer risk models: a comprehensive overview of existing models, validation, and clinical applications.

Numerous models have been developed to quantify the combined effect of various risk factors to predict either risk of developing breast cancer, risk of carrying a high-risk germline genetic mutation, specifically in the BRCA1 and BRCA2 genes, or the risk of both. These breast cancer risk models can be separated into those that utilize mainly hormonal and environmental factors and those that focus more on hereditary risk. Given the wide range of models from which to choose, understanding what each model predicts, the populations for which each is best suited to provide risk estimations, the current validation and comparative studies that have been performed for each model, and how to apply them practically is important for clinicians and researchers seeking to utilize risk models in their practice. This review provides a comprehensive guide for those seeking to understand and apply breast cancer risk models by summarizing the majority of existing breast cancer risk prediction models including the risk factors they incorporate, the basic methodology in their development, the information each provides, their strengths and limitations, relevant validation studies, and how to access each for clinical or investigative purposes.

Diagnostic and management challenges for MDM2-, CDK4-negative fatty tumors of the retroperitoneum.

BACKGROUND: Neoplasms of the retroperitoneum that contain a major fat component may represent either benign entities, such as lipomas or angiomyolipomas, or malignancy such as liposarcoma. Distinguishing these diagnoses has important implications for management. While liposarcomas often stain positively for MDM2 and CDK4 proteins, absence of these markers can lead to diagnostic and management challenges. METHODS: We examined three cases in our institution of fat-containing masses of the retroperitoneum that lacked MDM2 and CDK4 markers to highlight the challenges in diagnosing and managing these cases. A thorough review of the literature examining radiologic and histologic features that can be used to determine that diagnosis was conducted and summarized. RESULTS: The three cases we present represent the three main diagnostic entities that can be found in among fatty tumors of the retroperitoneum: lipoma, angiomyolipoma, and liposarcoma. While radiologic features and analysis of histology helped to inform management, these cases in conjunction with the literature also illustrate the limitations of the diagnostic work up and importance also factoring the biologic behavior of the tumor in its management. CONCLUSION: Fat-containing tumors of the retroperitoneum that do not stain for MDM2 or CDK4 can pose a diagnostic challenge. Assessing radiologic and pathologic features in conjunction with the biologic behavior of these tumors should inform their management.

Plasma-derived extracellular vesicle analysis and deconvolution enable prediction and tracking of melanoma checkpoint blockade outcome.

Immune checkpoint inhibitors (ICIs) show promise, but most patients do not respond. We identify and validate biomarkers from extracellular vesicles (EVs), allowing non-invasive monitoring of tumor- intrinsic and host immune status, as well as a prediction of ICI response. We undertook transcriptomic profiling of plasma-derived EVs and tumors from 50 patients with metastatic melanoma receiving ICI, and validated with an independent EV-only cohort of 30 patients. Plasma-derived EV and tumor transcriptomes correlate. EV profiles reveal drivers of ICI resistance and melanoma progression, exhibit differentially expressed genes/pathways, and correlate with clinical response to ICI. We created a Bayesian probabilistic deconvolution model to estimate contributions from tumor and non-tumor sources, enabling interpretation of differentially expressed genes/pathways. EV RNA-seq mutations also segregated ICI response. EVs serve as a non-invasive biomarker to jointly probe tumor-intrinsic and immune changes to ICI, function as predictive markers of ICI responsiveness, and monitor tumor persistence and immune activation.

An International Surgical Rotation as a Systems-Based Elective: The Botswana-University of Pennsylvania Surgical Experience.

OBJECTIVE: There is a growing need to address the global burden of surgical disease along with increasing interest in international surgical practice, necessitating an understanding of the challenges and issues that arise on a systems level when practicing abroad. DESIGN: This elective is a month-long rotation in which senior surgical residents participate in patient care as part of a surgical team in the main tertiary and teaching hospital in Gaborone, the capital city of Botswana. Clinical experience is combined with formal readings and educational sessions, with the attending surgeon supervising the program to develop a systems-based curriculum that contextualizes the clinical experience. A formal debriefing and written reflections by the residents at the conclusion of the rotation are used to qualitatively assess resident development and insight into systems-based international surgical practice. SETTING: Princess Marina Hospital, Gaborone, Botswana. PARTICIPANTS: General surgery residents in their fourth clinical year of training. RESULTS: Our elective met important requirements outlined in the literature for foreign practice, including adequate supervision of the American trainees and care to not detract from local trainees' educational experience. Residents' debriefing and written reflections demonstrated an increased understanding of systems-based practice and awareness of issues important to successful international surgical practice and collaboration. CONCLUSIONS: Our global surgery elective with a focus on systems-based practice sensitizes residents to the challenges and issues they must be aware of when practicing internationally.