JAMA Netw Open
December 2024
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Importance: Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific CBC.
Objective: To determine the association of deleterious germline variants in breast cancer susceptibility genes with ER-specific CBC development and whether ER status of the first primary breast cancer modifies these associations.
Design, Setting, And Participants: This case-control study included CBC cases and matched unilateral breast cancer controls from The Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based case-control study.
Nature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFDis Esophagus
January 2025
Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CAUSA.
Data on Barrett's esophagus (BE) and esophageal cancer (EC) outcomes in patients with eosinophilic esophagitis (EoE) are limited. We aimed to determine the risk of prevalent BE (<1 year after endoscopy), incident BE (≥1 year after endoscopy), and incident EC in patients with versus without EoE, and to identify predictors of BE/EC in EoE patients. We identified adult patients in the Merative MarketScan Database who underwent first-time upper endoscopy between 2008 and 2020.
View Article and Find Full Text PDFCancer Discov
January 2025
Stanford University, Stanford, California, United States.
Patients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 CAR T-cell (CAR22) in a phase 1b trial (NCT04088890).
View Article and Find Full Text PDFJ Pain Symptom Manage
December 2024
Wake Forest University School of Medicine, Winston-Salem, NC; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Context: Approximately 11% of cancer survivors smoke post-diagnosis.
Objective: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.
Methods: From 2017-2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.
Neuro Oncol
January 2025
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.
View Article and Find Full Text PDFSci Transl Med
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
Clin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFGut
December 2024
Biotech Research and Innovation Center (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Background And Objective: Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments.
View Article and Find Full Text PDFbioRxiv
December 2024
Stanford Blood Center, Stanford Health Care, Stanford, California, USA.
Background And Objectives: Apheresis platelets products and plasma are essential for medical interventions, but both still have inherent risks associated with contamination and viral transmission. Platelet products are vulnerable to bacterial contamination due to storage conditions, while plasma requires extensive screening to minimize virus transmission risks. Here we investigate rapid irradiation to sterilizing doses for bacteria and viruses as an innovative pathogen reduction technology.
View Article and Find Full Text PDFAm J Hematol
December 2024
Fred Hutchinson Cancer Research Center, Seattle, Washington State, USA.
Genetics
December 2024
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. Recognizing the biases inherent to GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
December 2024
National Comprehensive Cancer Network.
Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
December 2024
National Comprehensive Cancer Network.
The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.
View Article and Find Full Text PDFCancer Chemother Pharmacol
December 2024
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, USA.
Progressive leptomeningeal metastases (LM) are associated with intractable neurological symptoms and a poor prognosis, and effective treatment options are limited. Intrathecal (IT) pemetrexed has been shown to confer clinical benefit in lung adenocarcinoma, yet our understanding of the efficacy and safety of the treatment is limited. We report a patient with a long-standing history of leptomeningeal disease due to ALK-positive adenocarcinoma of the lung, previously controlled by increased doses of lorlatinib (125 mg/day).
View Article and Find Full Text PDFJBMR Plus
January 2025
Department of Medicine, Division of Endocrinology, Stanford University, Stanford, CA 94305, United States.
Germline and somatic pathogenic variants in the gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for -related conditions, including deletion, truncating, missense, and splice site mutations.
View Article and Find Full Text PDFSemin Thorac Cardiovasc Surg
December 2024
Division of Thoracic Surgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA. Electronic address:
The Clinical Practice Standards Committee of the American Association for Thoracic Surgery assembled an expert panel and conducted a systematic review of the literature detailing studies directly comparing treatment options for high-risk patients with stage I non-small cell lung cancer (NSCLC). A systematic search was performed to identify publications comparing outcomes following image-guided thermal ablation (IGTA), stereotactic ablative radiotherapy (SABR), and sublobar resection-the main treatment options applicable to high-risk patients with stage I NSCLC. There were no publications detailing completed randomized controlled trials comparing these treatment options.
View Article and Find Full Text PDFSemin Thorac Cardiovasc Surg
December 2024
Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, and UPMC Hillman Cancer Center. Pittsburgh, PA. Electronic address:
Stereotactic ablative radiotherapy (SABR) has emerged as an alternative, non-surgical treatment for high-risk patients with stage I non-small cell lung cancer (NSCLC) with increased use over time. The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) assembled an expert panel and conducted a systematic review of the literature evaluating the results of SABR, which is also referred to as stereotactic body radiation therapy (SBRT) or stereotactic radiosurgery (SRS), prior to developing treatment recommendations for high-risk patients with stage I NSCLC based on expert consensus. Publications detailing the findings of 16 prospective studies of SABR and 14 retrospective studies of SABR for the management of early-stage lung cancer in 54 697 patients were identified by systematic review of the literature with further review by members of our expert panel.
View Article and Find Full Text PDFSemin Thorac Cardiovasc Surg
December 2024
Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, and UPMC Hillman Cancer Center. Pittsburgh, PA. Electronic address:
Sublobar resection offers a parenchymal-sparing surgical alternative to lobectomy and includes wedge resection and segmentectomy. Sublobar resection has been historically utilized in high-risk patients with compromised lung function; however, the technique is becoming more prevalent for normal-risk patients with peripheral lung tumors < 2 cm. In this article, we summarize the technique of sublobar resection, the importance of surgical margins and lymph node sampling, patient selection, perioperative complications, outcomes, and the impact of sublobar resection on the quality of life.
View Article and Find Full Text PDFJNCI Cancer Spectr
January 2025
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, United States.
Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.
View Article and Find Full Text PDFNat Biotechnol
December 2024
Department of Chemistry, Stanford University, Stanford, CA, USA.
Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions.
View Article and Find Full Text PDFSemin Thorac Cardiovasc Surg
December 2024
Division of Thoracic Surgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA. Electronic address:
Nat Struct Mol Biol
December 2024
Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.
View Article and Find Full Text PDFJAMA Oncol
December 2024
Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.
Importance: Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.
Objective: To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.
Semin Thorac Cardiovasc Surg
December 2024
Division of Thoracic Surgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA. Electronic address:
Objective: A significant proportion of patients with stage I non-small cell lung cancer (NSCLC) are considered at high risk for complications or mortality after lobectomy. The American Association for Thoracic Surgery (AATS) previously published an expert consensus document detailing important considerations in determining who is at high risk. The current objective was to evaluate treatment options and important factors to consider during treatment selection for these high-risk patients.
View Article and Find Full Text PDF© LitMetric 2025. All rights reserved.