3754 hot topic(s) found with the query "Cancer"
Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma
J Xu et al, JPM, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment."
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
J Xin et al, Nature Comm, April 8, 2024
(Posted: Apr 09, 2024 8AM)
From the abstract: "The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD?=?1.99, P?=?1.76?×?10-8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P?=?3.21?×?10-14; 543 patients) and 1.80 (P?=?1.11?×?10-9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. "
Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies.
Ariadna Tibau et al. JAMA Oncol 2024 4
(Posted: Apr 05, 2024 9AM)
From the abstract: "What is the validity of the molecular targets and clinical benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the results of pivotal clinical trials? In this cohort study, 50 molecular-targeted drugs covering 84 indications were identified. Using an international grading system to evaluate molecular targetability strength (European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets) and a scale to assess clinical benefit in genome-targeted cancer therapies (European Society for Medical Oncology Magnitude of Clinical Benefit Scale), 24 indications (29%) supported high-benefit genomic-based cancer treatments. The therapeutic benefit grading frameworks used in this study can help stakeholders identify therapies with the greatest clinical potential. "
Strategies to improve implementation of cascade testing in hereditary cancer syndromes: a systematic review
J Chiang et al, NPJ Genomic Medicine, April 5, 2024
(Posted: Apr 04, 2024 9AM)
From the abstract: " Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. This systematic review shows that most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream."
Socioecologic Factors and Racial Differences in Breast Cancer Multigene Prognostic Scores in US Women.
Ashwini Z Parab et al. JAMA Netw Open 2024 4 (4) e244862
(Posted: Apr 04, 2024 9AM)
From the abstract: " In this cohort study of 69?139 women with breast cancer, non-Hispanic Black and non-Hispanic American Indian and Alaska Native women were more likely to have tumors with high-risk RSs compared with non-Hispanic White women. For non-Hispanic Black women, area-level socioeconomic position, urban residence, and insurance status mediated 17% of the racial difference in the RSs, and racial differences between non-Hispanic Black and non-Hispanic White women in the RSs were observed only among urban women. These findings suggest that disproportionately aggressive breast tumor biology among non-Hispanic Black women may be partially explained by socioecologic factors."
Challenges and opportunities for Lynch syndrome cascade testing in the United States.
Lauren E Passero et al. Fam Cancer 2024 3
(Posted: Apr 02, 2024 10AM)
From the abstract: " Lynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and environmental barriers including a shortage of genetics professionals, high costs, and fears of discrimination also reduce cascade testing. These multi-level barriers may disproportionately impact underserved populations in the United States,"
Utilizing geospatial artificial intelligence to map cancer disparities across health regions
A Fadiel et al, Sci Report, April 2, 2024
(Posted: Apr 02, 2024 9AM)
From the abstract: "We have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities. iCAT allows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms. "
What to Know About Lynch Syndrome
ThedaCare Genetic Counseling, March 2024
(Posted: Apr 01, 2024 9AM)
From the article: " While it is impossible to change our genes, with knowledge comes power. In the case of Lynch syndrome, a genetic condition that can increase a person’s risk for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening, as well as genetic testing, when recommended."
Deep learning in cancer genomics and histopathology
M Unger et al, Genome Medicine, March 27, 2024
(Posted: Mar 27, 2024 1PM)
From the abstract: " Histopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. "
Secondary use of genomic data: patients’ decisions at point of testing and perspectives to inform international data sharing
M Martyn et al, EJHG, March 25, 2024
(Posted: Mar 25, 2024 8AM)
From the abstract: "International sharing of genomic data files arising from clinical testing of patients is essential to further improve genomic medicine. Whilst the general public are reluctant to donate DNA for research, the choices patients actually make about sharing their clinical genomic data for future re-use (research or clinical) are unknown. We ascertained the data-sharing choices of 1515 patients having genomic testing for inherited conditions or cancer treatment from clinical consent forms. "
PARP Inhibitors for Breast Cancer Treatment: A Review.
Stefania Morganti et al. JAMA Oncol 2024 3
(Posted: Mar 23, 2024 6AM)
From the abstract: "Poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients. This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. "
Lynch Syndrome Ups Risk for Colorectal, Other Cancers
E Herlache, Cancer Care, March 2024
(Posted: Mar 23, 2024 6AM)
From the article: "It’s impossible to change our genes, but with knowledge comes power. In the case of Lynch syndrome, a genetic condition that ups people’s risks for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening as well as genetic testing, when warranted. Lynch syndrome puts a person at a higher risk of developing colorectal, uterine, and ovarian cancer. It’s also associated with other cancers, including kidney, stomach, bladder, brain, prostate, and pancreatic cancer. "
The promise of AI in personalized breast cancer screening: are we there yet?
Despina Kontos et al. Nat Rev Clin Oncol 2024 3
(Posted: Mar 21, 2024 7AM)
From the abstract: " The benefits and potential harms of mammography-based screening for breast cancer are often a matter of debate. Here, I discuss the promises and limitations of a recent study that tested an artificial intelligence-based tool for the detection of breast cancer in digital mammograms in a large, prospective screening setting."
Training Institute for Dissemination and Implementation Research in Genomics and Precision Public Health (TIDR-GPPH)
UNC Precision Public Health Network, March 2024
(Posted: Mar 20, 2024 7AM)
From the website: "This facilitated course is intended to provide participants with a thorough grounding in conducting dissemination and implementation (D&I) research with a specific focus on genomics and precision public health.is. TIDIR-GPPH will be a hybrid course including training through open access Training Institute for Dissemination and Implementation Research in Cancer (TIDIRC) with assigned reading material and office hours and a 2-day in-person event. Faculty and guest lecturers consist of leading experts in D&I theories, models, and frameworks; intervention fidelity and adaptation; stakeholder engagement and partnership for D&I; research methods and study designs for D&I; and measures and outcomes for D&I. "
Cell-free DNA for Colorectal Cancer Screening.
Y M Dennis Lo et al. N Engl J Med 2024 3 (11) 1047-1050
(Posted: Mar 14, 2024 10AM)
From the article: "A recent study demonstrated the feasibility of using plasma cfDNA to screen for colorectal cancer, but the relatively low sensitivity for the detection of advanced precancerous lesions is a limitation. Moreover, colonoscopy not only detects such lesions with high sensitivity but also permits their immediate removal. The noninvasiveness (relatively speaking) of the plasma cfDNA assay, though, is a feature that seems likely to result in greater uptake than colonoscopy."
Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening.
Thomas F Imperiale et al. N Engl J Med 2024 3 (11) 984-993
(Posted: Mar 14, 2024 10AM)
From the abstract: "In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. "
Improving Noninvasive Colorectal Cancer Screening.
John M Carethers et al. N Engl J Med 2024 3 (11) 1045-1046
(Posted: Mar 14, 2024 10AM)
From the article: "Screening for colorectal cancer saves lives. Screening tests have evolved to include stool-based, endoscopic and image-based, and blood-based methods, with minimal thresholds for sensitivity and specificity for colorectal cancer set by the baseline characteristics of FIT. Although multiple tests have been developed over time and vary in cost-effectiveness for colorectal cancer screening, the best screening test is the one that gets completed by the patient. Most of the recommended tests, including the two newer tests assessed in the studies now published in the Journal, improve on the sensitivity and approach the specificity of FIT. "
A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.
Daniel C Chung et al. N Engl J Med 2024 3 (11) 973-983
(Posted: Mar 14, 2024 10AM)
From the abstract: "We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. This cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions."
Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.
Todd M Gibson et al. Nat Med 2024 3
(Posted: Mar 12, 2024 0PM)
From the abstract: "Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR?=?1.37, 95% confidence interval (CI)?=?1.29–1.46), female breast cancer (OR?=?1.42, 95% CI?=?1.27–1.58), thyroid cancer (OR?=?1.48, 95% CI?=?1.31–1.67), squamous cell carcinoma (OR?=?1.20, 95% CI?=?1.00–1.44) and melanoma (OR?=?1.60, 95% CI?=?1.31–1.96) "
Dozens of precision cancer drugs tested at lower doses to reduce side effects and cut costs.
Sofia Moutinho et al. Nat Med 2024 3
(Posted: Mar 11, 2024 11AM)
From the abstract: "Growing evidence shows that lower doses or shorter treatments of precision cancer therapies could reduce toxicity and save money — but more clinical trials are needed. "
Health-Related quality of life and DNA Methylation-Based aging biomarkers among survivors of childhood cancer.
Noel-Marie Plonski et al. J Natl Cancer Inst 2024 3
(Posted: Mar 07, 2024 8AM)
From the abstract: "Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related-quality-of-life (HRQOL). However, associations between DNA methylation (DNAm)-based aging biomarkers and HRQOL have not been evaluated. DNAm was generated with Infinium EPIC BeadChip on blood-derived DNA (median[range] for age at blood draw?=?34.5[18.5-66.6] years) and HRQOL was assessed with age at survey (32.3[18.4-64.5] years) from 2,206 survivors in the St Jude Lifetime Cohort. "
A gut microbial signature for combination immune checkpoint blockade across cancer types.
Ashray Gunjur et al. Nat Med 2024 3
(Posted: Mar 03, 2024 10AM)
From the abstract: "We performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB (n?=?106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. "
Genomic risk scores in prostate cancer: polygenic yes, but are they poly-ancestral?
Arnab Basu et al. J Natl Cancer Inst 2024 2
(Posted: Feb 22, 2024 9AM)
From the article: "Today, these new studies are providing critical data necessary to update our risk evaluation tools in an intentionally inclusive way and advance the quality of care for all patients with prostate cancer. A recent study focuses on germline risk scores for prostate cancer diagnosis, but closer investigation of genomic data holds the promise of improving outcomes for patients of African ancestry at all stages of their disease course. "
Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer.
Qingyang Xiao et al. J Natl Cancer Inst 2024 2
(Posted: Feb 22, 2024 9AM)
From the abstract: "We used women from two Swedish cohorts (KARMA and pKARMA), including 28,362 women with genotyping data and 13,226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133,389 first-degree relatives. Associations between protein-truncating variants (PTVs) in 8 risk genes and breast cancer polygenic risk score (PRS) in index women and cancer risks among their relatives were modeled via Cox regression.Female relatives of index women who were PTV carriers in any of the 8 risk genes had an increased breast cancer risk compared to those of non-carriers (HR 1.85, 95% CI: 1.52-2.27), with the strongest association found for PTVs in BRCA1/2. "
Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations
NJ Lennon et al, Nature Medicine, February 19, 2024
(Posted: Feb 20, 2024 7AM)
From the abstract: " From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. "
Understanding perceptions of tumor genomic profile testing in Black/African American cancer patients in a qualitative study: the role of medical mistrust, provider communication, and family support
CC Luck et al, J Comm Genetics, Feb 16, 2024
(Posted: Feb 16, 2024 4PM)
From the abstract: "Tumor genomic profiling (TGP) examines genes and somatic mutations specific to a patient’s tumor to identify targets for cancer treatments but can also uncover secondary hereditary (germline) mutations. Most patients are unprepared to make complex decisions related to this information. Black/African American (AA) cancer patients are especially at risk because of lower health literacy, higher levels of medical mistrust, and lower awareness and knowledge of genetic testing. But little is known about their TGP attitudes or preferences. "
Identification of people with Lynch syndrome from those presenting with colorectal cancer in England: baseline analysis of the diagnostic pathway
FE McRonald et al, EJHG, February 15, 2024
(Posted: Feb 15, 2024 9AM)
From the abstract: "Only 44% of CRCs were screened for dMMR; these figures varied over four-fold with respect to geography. Of those CRCs identified as dMMR, only 51% underwent subsequent diagnostic testing. Overall, only 1.3% of patients with colorectal cancer had a germline MMR genetic test performed; up to 37% of these tests occurred outside of NICE guidelines. The low rates of molecular diagnostic testing in CRC support the premise that Lynch syndrome is underdiagnosed, with significant attrition at all stages of the testing pathway. "
Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.
Fangjian Guo et al. JAMA Netw Open 2024 2 (2) e2356078
(Posted: Feb 15, 2024 9AM)
From the abstract: "Is a population-wide genetic testing strategy more cost-effective than the current family history–based testing strategy for breast and ovarian cancer prevention? This economic evaluation found that population-based BRCA1, BRCA2, and PALB2 testing among unselected women was cost-effective for the prevention of breast and ovarian cancer and remained cost-effective in extensive 1-way sensitivity analyses. Population-wide genetic testing was 100% cost-effective for all the simulations in probabilistic sensitivity analyses; it became cost-inefficient only when the cost of the test exceeded a certain threshold ($825). The findings support the need for a shift toward more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management. "
Deep learning models across the range of skin disease.
Kaushik P Venkatesh et al. NPJ Digit Med 2024 2 (1) 32
(Posted: Feb 13, 2024 9AM)
From the abstract: "We explore the evolving landscape of diagnostic artificial intelligence (AI) in dermatology, particularly focusing on deep learning models for a wide array of skin diseases beyond skin cancer. We critically analyze the current state of AI in dermatology, its potential in enhancing diagnostic accuracy, and the challenges it faces in terms of bias, applicability, and therapeutic recommendations. "
Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.
Xia Wei et al. JAMA Netw Open 2024 2 (2) e2355324
(Posted: Feb 11, 2024 10AM)
From the abstract: This economic evaluation using a decision-analytic Markov model with a simulated cohort of women aged 30 years found that undergoing both risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was most cost-effective, maximizing cancers prevented for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) pathogenic variants, while RRSO was cost-effective at age 45 years for women with RAD51C, RAD51D, and BRIP1 pathogenic variants." "
Racial and ethnic disparities in genomic testing among lung cancer patients: a systematic review.
Clare Meernik et al. J Natl Cancer Inst 2024 2
(Posted: Feb 11, 2024 10AM)
From the abstract: "We conducted a systemic review to examine racial and ethnic disparities in the use of genomic testing among lung cancer patients in the U.S. Two comprehensive searches in PubMed, Embase, and Scopus were conducted (September 2022, May 2023). Original studies that assessed rates of genomic testing by race or ethnicity were included. A majority of studies, though not all, observed racial and ethnic disparities in the use of genomic testing among patients with lung cancer. Heterogeneity of study results throughout a period of changing clinical guidelines suggests that minoritized populations—Black patients in particular—have faced additional barriers to genomic testing."
Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families
WK Ho et al, Lancet Regional Health, February 2024
(Posted: Feb 06, 2024 1PM)
From the abstract: " Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. We found that the absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management."
Combining rare and common genetic variants improves population risk stratification for breast cancer
A Bolze et al, Genetics in Medicine Open, February 2, 2024
(Posted: Feb 05, 2024 11AM)
From the abstract: " This study aimed to evaluate the performance of different genetic screening approaches to identify women at high-risk of breast cancer in the general population. We retrospectively studied 25,591 women with available electronic health records and genetic data, participants in the Healthy Nevada Project. Family history of breast cancer was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this risk assessment method is not being properly utilized for early screening. Genetics offered an alternative method for risk assessment. 11.4% of women were identified as high-risk based on possessing a predicted loss-of-function (pLOF) variant in BRCA1, BRCA2 or PALB2 (hazard ratio = 10.4, 95% confidence interval: 8.1-13.5), or a pLOF variant in ATM or CHEK2 (HR = 3.4, CI: 2.4-4.8), or being in the top 10% of the polygenic risk score (PRS) distribution (HR = 2.4, CI: 2.0-2.8). "
Maximizing scarce colonoscopy resources: the crucial role of Stool-Based tests.
Gloria D Coronado et al. J Natl Cancer Inst 2024 2
(Posted: Feb 04, 2024 4PM)
From the abstract: "During the COVID-19 pandemic, health systems, including federally qualified health centers (FQHCs), experienced disruptions in colorectal cancer (CRC) screening. National organizations called for greater use of at-home stool-based testing followed by colonoscopy for those with abnormal test results to limit (in-person) colonoscopy exams to people with acute symptoms, or who were high-risk. This ‘stool-test-first’ strategy may also be useful for adults with low-risk adenomas who are due for surveillance colonoscopy. "
Forget lung, breast or prostate cancer: why tumour naming needs to change The conventional way of classifying metastatic cancers according to their organ of origin is denying people access to drugs that could help them.
F Andre et al, Nature, January 31, 2024
(Posted: Feb 01, 2024 9AM)
From the article: " Over the past century, the two main approaches to treating people with cancer — surgery and radiation — have focused on where in the body the tumour is. This has led to medical oncologists and other health-care providers, regulatory agencies, insurance companies, drug firms — and patients — categorizing cancers according to the organ in which the tumour originated. Yet there is a growing disconnect between classifying cancers in this way and developments in precision oncology, which uses the molecular profiling of tumour and immune cells to guide therapies."
Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma
L Jiang et al, Nature Medicine, January 29, 2024
(Posted: Jan 29, 2024 8AM)
From the abstract: "Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. "
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort.
Wade T Iams et al. JAMA Netw Open 2024 1 (1) e2351700
(Posted: Jan 23, 2024 7AM)
In this cohort study of 3209 patients undergoing concurrent testing across 4 cancer types who received both tissue-based and ctDNA genomic profiling results, 45.1% had a guideline-based variant detected. Of these patients, 9.3% had a clinically actionable variant detected by ctDNA profiling that was not detected by solid-tissue testing, and 24.2% had a variant detected by solid-tissue testing but not by ctDNA profiling; for patients with breast cancer with actionable variants, 20.2% had a unique, guideline-based variant detected by ctDNA profiling; most (55.0%) of these unique ctDNA variants were in the ESR1 gene.
The study suggests that concurrent ctDNA–based and tissue-based genomic profiling identified more patients with targetable, guideline-based variants than would have been discovered by tissue profiling alone, with a higher detection rate among patients with breast cancer. "
Concurrent Circulating Tumor DNA and Tissue Genotyping-Ready for Prime Time?
Benjamin A Bleiberg et al. JAMA Netw Open 2024 1 (1) e2351679
(Posted: Jan 23, 2024 7AM)
From the article: "Cell-free circulating tumor DNA (ctDNA) is shed by tumor cells into the systemic circulation and, thanks to advancements in next-generation sequencing (NGS) technologies, affords the opportunity to noninvasively detect cancer-specific somatic variants. The use of ctDNA-based molecular genotyping for tumor profiling and identification of patients eligible for targeted therapies has been integrated into clinical practice for a variety of tumor types. The prime example of this is in non–small cell lung cancer (NSCLC), where identifying actionable variants via genomic profiling is essential to determining the appropriate standard of care for patients. "
Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry.
Kyung Min Lee et al. J Natl Cancer Inst 2024 1
(Posted: Jan 20, 2024 10AM)
From the abstract: "This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male Veterans using two-sided tests. Our analysis included 36,717 Veterans (10,297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; p?<?.001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (OR 2.18, 95% CI 1.93-2.47), but the effect was stronger among men of European descent (OR 3.89, 95% CI 3.62-4.18). "
Landmark national study supports use of whole genome sequencing in standard cancer care
Genomics England, January 2023
(Posted: Jan 14, 2024 10AM)
From the website: "In the largest study of its kind, scientists today report how combining health data with whole genome sequence (WGS) data in patients with cancer can help doctors provide more tailored care for their patients. The research shows that linking WGS data to real-world clinical data can identify changes in cancer DNA that may be relevant for an individual patient’s care, for example by helping identify what treatment might work best for them based on their cancer. "
Remembering My Brother Who Died of Cancer January 11, 2024 Georgia Hurst Blog Article
G Hurst, Cure, January 11, 2024
(Posted: Jan 14, 2024 10AM)
From the article: "Today marks what would have been my brother Jimmy's 65th birthday. It's a bittersweet moment filled with both celebration and reflection as I remember the incredible person he was and the battle he faced against colorectal cancer caused by Lynch syndrome. In sharing this story, I hope to raise awareness about Lynch syndrome, honor Jimmy's memory and shed light on the challenges of survivor guilt that often accompany the loss of a loved one due to Lynch syndrome. "
Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme
A Sosinsky et al, Nature Medicine, January 11, 2024
(Posted: Jan 11, 2024 7AM)
From the abstract: "We analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). "
Lung cancer in patients who have never smoked - an emerging disease.
Jaclyn LoPiccolo et al. Nat Rev Clin Oncol 2024 1
(Posted: Jan 11, 2024 7AM)
From the abstract: " New data have provided important insights into the molecular and genomic characteristics of LCINS, which are distinct from those of smoking-associated lung cancers and directly affect treatment decisions and outcomes. Herein, we review the emerging data regarding the aetiology and features of LCINS, particularly the genetic and environmental underpinnings of this disease as well as their implications for treatment. "
The Potential of Genetics in Identifying Women at Lower Risk of Breast Cancer.
Alexandre Bolze et al. JAMA Oncol 2023 12
(Posted: Jan 02, 2024 10AM)
From the abstract: "Can genetic information identify women for whom it is safe to delay mammogram screening? In this case-control study of 25?591 women, 2338 (9.1%) were classified as having low genetic risk for breast cancer; these women exhibited significantly later onset of breast cancer compared with average-risk or high-risk counterparts, indicating a potential to defer mammogram screening by 5 to 10 years. Delaying the age to start mammogram screenings for women at low genetic risk could optimize health care resource allocation.
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Secondary (additional) findings from the 100,000 Genomes Project: disease manifestation, healthcare outcomes and costs of disclosure
J Nolan et al, Genetics in Medicine, December 19, 2023
(Posted: Dec 20, 2023 9AM)
From the abstract: "The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia, von Hippel-Lindau. Here we report disclosure processes, manifestation of AF-related disease, outcomes and costs. "
How Holiday Conversations About Cancer Can Save Lives
G Hurst, Cure, December 13, 2023
(Posted: Dec 17, 2023 3PM)
From the article: "Silently plaguing our family is Lynch syndrome, a hereditary cancer syndrome that increases the risk of developing various cancers. This genetic predisposition often goes undetected, affecting approximately 1 in 279 Americans. Lynch syndrome arises from mutations in genes responsible for DNA error repair, potentially leading to tumor formation and triggering cancer. Knowing your family history of Lynch syndrome can be a life-saving intervention. Sadly, it took two of my brothers to develop cancer before I became aware of it. Early detection and screening have reduced my risk of developing cancer and since my diagnosis of having Lynch syndrome, treatment options for those who develop Lynch syndrome cancers have advanced considerably. "
Pregnancy After Breast Cancer in Young BRCA Carriers An International Hospital-Based Cohort Study
M Lambertini et al, JAMA Network Open, December 7, 2023
(Posted: Dec 08, 2023 2PM)
From the abstract: "Among women carrying germline BRCA pathogenic variants, is pregnancy after breast cancer associated with adverse maternal or fetal outcomes? This international, hospital-based, retrospective cohort study including 4732 BRCA carriers showed that 1 in 5 patients conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with adverse maternal prognosis or fetal outcomes.
The cumulative incidence of pregnancy after breast cancer and disease-free survival in this large international cohort of young BRCA carriers may inform care for affected patients. "
Machine learning improves prediction of clinical outcomes for invasive breast cancers.
et al. Nat Med 2023 11
(Posted: Dec 01, 2023 7AM)
From the article: " A prognostic model for invasive breast cancer that is based on interpretable measurements of epithelial, stromal, and immune components outperforms histologic grading by expert pathologists. This model could improve clinical management of patients diagnosed with invasive breast cancer and address the concerns of pathologists about artificial intelligence (AI) trustworthiness by providing transparent and explainable predictions."
Latina immigrants' breast and colon cancer causal attributions: genetics is key.
Katie Fiallos et al. J Community Genet 2023 11
(Posted: Dec 01, 2023 7AM)
From the abstract: "Participants answered semi-structured, open-ended questions regarding the risk factors and rankings. Interviews were transcribed and subjected to thematic analysis. CCA showed no consensus around rank of causes for either cancer, and residual agreement analysis suggested the presence of two subcultural groups. “Genetics” and “hereditary factors” ranked first and second on average across participants for both cancers. Based on interview data, participants were less aware of colon cancer than breast cancer. Participants’ endorsement of heredity as a cause of breast and colon cancer was similar to beliefs reported in studies of primarily non-Latina populations. "
Primary Care Provider Receptivity to Multi-Cancer Early Detection Test Use in Cancer Screening
CV Chambers et al, JPM, November 2023
(Posted: Nov 30, 2023 9AM)
From the abstract: "Multi-cancer early detection tests (MCEDs) are blood-based tests that detect biomarkers released or induced by cancer cells. If MCED tests are shown to be safe and effective in cancer screening, they are likely to be ordered and managed in primary care. To understand primary care providers’ support for and concerns about the implementation and management of MCED testing, the research team developed a cross-sectional survey that was sent to 939 primary care providers (physicians, residents/fellows, and advanced practice providers) in a large academic health system. "
A population-level digital histologic biomarker for enhanced prognosis of invasive breast cancer.
Mohamed Amgad et al. Nat Med 2023 11
(Posted: Nov 29, 2023 9AM)
From the abstract: " Here we present the Histomic Prognostic Signature (HiPS), a comprehensive, interpretable scoring of the survival risk incurred by breast tumor microenvironment morphology. HiPS uses deep learning to accurately map cellular and tissue structures to measure epithelial, stromal, immune, and spatial interaction features. It was developed using a population-level cohort from the Cancer Prevention Study-II and validated using data from three independent cohorts."
Navigating epigenetic epidemiology publications
W Yu et al, BMC Epig Comm, November 22, 2023,
(Posted: Nov 27, 2023 11AM)
From the abstract: "Since its beginning more than 75 years ago, epigenetics has been an evolving field with growing applications to the study of cancer, aging, and gene expression in response to environmental exposures. The emergence of high-throughput technology for measuring epigenetic markers has enabled population-based studies. The relatively new field of epigenetic epidemiology investigates epigenetic associations from a population perspective for insights into disease risk, prevention, and progression. "
Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159
(Posted: Nov 14, 2023 8AM)
From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "
Combined population genomic screening for three high-risk conditions in Australia: a modelling study
P Lacaze et al, e Clin Medicine, November 2023
(Posted: Nov 11, 2023 4PM)
From the abstract: "This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. "
Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.
William C Chen et al. Nat Med 2023 11
(Posted: Nov 10, 2023 7AM)
From the abstract: "Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N?=?1856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared to all other systems tested (N?=?9) in the clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). "
Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.
Brittany D Jenkins et al. JAMA Netw Open 2023 11 (11) e2341651
(Posted: Nov 06, 2023 6PM)
From the abstract: "What is the association between neighborhood deprivation, DNA methylation, and gene expression in breast tissue for Black and White women with breast cancer? In a cross-sectional study of 185 women with breast cancer, higher neighborhood deprivation was associated with decreased methylation and gene expression of 2 tumor suppressor genes, LRIG1 and WWOX, for Black patients with breast cancer. These findings suggest that, for Black women, high neighborhood deprivation is associated with epigenetic differences in breast tumors that may lead to more aggressive disease, signaling the need for continued investment in public health interventions and policy changes at the neighborhood level. "
Computational immunogenomic approaches to predict response to cancer immunotherapies.
Venkateswar Addala et al. Nat Rev Clin Oncol 2023 11
(Posted: Nov 03, 2023 8AM)
From the abstract: " Cancer immunogenomics is an emerging field that bridges genomics and immunology. The establishment of large-scale genomic collaborative efforts along with the development of new single-cell transcriptomic techniques and multi-omics approaches have enabled characterization of the mutational and transcriptional profiles of many cancer types and helped to identify clinically actionable alterations as well as predictive and prognostic biomarkers. Researchers have developed computational approaches and machine learning algorithms to accurately obtain clinically useful information from genomic and transcriptomic sequencing data. "
Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.
John V Heymach et al. N Engl J Med 2023 10 (18) 1672-1684
(Posted: Nov 02, 2023 9AM)
From the abstract: "Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non–small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcome. 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). Perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. "
Applications of Liquid Biopsy for Surgical Patients With Cancer: A Review.
Kelly M Mahuron et al. JAMA Surg 2023 11
(Posted: Nov 01, 2023 1PM)
From the abstract: "Liquid biopsy analytes such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been the most clinically studied assays and were initially limited to advanced-stage disease. In the metastatic setting, CTCs and ctDNA levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. "
From a Fledgling Genetic Science, A Murky Market for Prediction
A Smart, Undark, October 27, 2023
(Posted: Oct 27, 2023 4PM)
From the article: "Although polygenic scores alone may not be powerful predictors of disease, many researchers are optimistic that they can be combined with other, more conventional methods of risk estimation to improve screening for common conditions like cancer, cardiovascular diseases, and diabetes.
At the same time, however, a chorus of experts say that society should temper any expectations that polygenic scores will revolutionize health care. "
Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk.
Xuechen Chen et al. JAMA Netw Open 2023 10 (10) e2339670
(Posted: Oct 27, 2023 9AM)
From the abstract: "How can risk variation in individuals without a family history of colorectal cancer (CRC) be translated into personalized starting ages of screening? In this cohort study of 242?779 participants with no previous screening for and no family history of CRC, derivation of risk-adapted starting ages of screening used 2 major CRC risk indicators, sex and a polygenic risk score (PRS), based on the risk advancement period concept. Risk-adapted starting ages varied by as much as 24 years between men in the highest PRS decile and women in the lowest PRS decile, even among individuals at average risk. "
Predicting Breast Cancer Risk Using Radiomics Features of Mammography Images
Y Suzuki et al, JPM< October 24, 2023
(Posted: Oct 25, 2023 9AM)
From the abstract: " Mammography images contain a lot of information about not only the mammary glands but also the skin, adipose tissue, and stroma, which may reflect the risk of developing breast cancer. We aimed to establish a method to predict breast cancer risk using radiomics features of mammography images and to enable further examinations and prophylactic treatment to reduce breast cancer mortality. We used mammography images of 4000 women with breast cancer and 1000 healthy women from the ‘starting point set’ of the OPTIMAM dataset, a public dataset."
Multitarget Stool RNA Test for Colorectal Cancer Screening.
Erica K Barnell et al. JAMA 2023 10
(Posted: Oct 24, 2023 2PM)
From the abstract: " What is the performance of the novel multitarget stool RNA (mt-sRNA) test (ColoSense) for individuals 45 years and older undergoing colorectal cancer screening? A pivotal prospective, cross-sectional clinical trial comprising 8920 eligible participants was used to evaluate the sensitivity and specificity of the mt-sRNA test compared with a colonoscopy. The sensitivity of the mt-sRNA test for detecting colorectal cancer was 94%, the sensitivity for detecting advanced adenomas was 46%, and the specificity for no lesions on colonoscopy was 88%."
Inborn errors of immunity: an expanding universe of disease and genetic architecture.
Yemsratch T Akalu et al. Nat Rev Genet 2023 10
(Posted: Oct 23, 2023 7PM)
From the abstract: "Inborn errors of immunity (IEIs) are generally considered to be rare monogenic disorders of the immune system that cause immunodeficiency, autoinflammation, autoimmunity, allergy and/or cancer. Here, we discuss evidence that IEIs need not be rare disorders or exclusively affect the immune system. Namely, an increasing number of patients with IEIs present with severe dysregulations of the central nervous, digestive, renal or pulmonary systems. "
Liquid biopsy epigenomic profiling for cancer subtyping.
Sylvan C Baca et al. Nat Med 2023 10
(Posted: Oct 23, 2023 8AM)
From the abstract: " Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1?ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. "
Personalized anti-cancer vaccine combining mRNA and immunotherapy tested in melanoma trial.
Thiago Carvalho et al. Nat Med 2023 9 (10) 2379-2380
(Posted: Oct 19, 2023 2PM)
From the article: "An estimated 325,000 new cases of malignant melanoma were diagnosed worldwide in 2020. The clinical deployment of immune checkpoint inhibitors over the past 12 years has revolutionized melanoma treatment, and the 5-year survival rate in the USA now approaches 95%. However, the frequency of melanoma is increasing, particularly in lighter-skinned people, and for the minority of patients diagnosed with metastatic disease, the 5-year survival rate is 35%, although the introduction of immunotherapy has doubled the median survival time for these patients. "
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.
Emily C Harrold et al. Nat Med 2023 10 (10) 2458-2463
(Posted: Oct 19, 2023 2PM)
From the abstract: "Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received =1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21?months (interquartile range, 6–38). "
“I just wanted more”: Hereditary cancer syndromes patients’ perspectives on the utility of circulating tumour DNA testing for cancer screening
EA Wauran et al, EJHG, October 11, 2023
(Posted: Oct 12, 2023 9AM)
From the abstract: "Thirty HCS patients were interviewed (n?=?19 women, age range 20s-70s, n?=?25 were white). Participants were highly concerned about developing cancers, particularly those without reliable screening options for early detection. They “just wanted more” than their current screening strategies. Participants were enthusiastic about ctDNA’s potential to be comprehensive (detect multiple cancers), predictive (detect cancers early) and tailored (lead to personalized clinical management). Participants also acknowledged ctDNA’s potential limitations, including false positives/negatives risks and experiencing additional anxiety. "
Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study
D Shrag et al. The Lancet, October 7, 2023
(Posted: Oct 06, 2023 7AM)
From the abstract: "Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. The study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility. "
Heterogeneity and treatment landscape of ovarian carcinoma.
Ana C Veneziani et al. Nat Rev Clin Oncol 2023 10
(Posted: Oct 06, 2023 7AM)
From the abstract: "Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. "
Big advocacy, little recognition: the hidden work of Black patients in precision medicine
LH Jerido et al, J Comm Genetics, October 2023
(Posted: Oct 03, 2023 9AM)
From the abstract: " As cost-effective next-generation genome sequencing rapidly develops, calls for greater inclusion of Black people in genomic research, policy, and practice are necessary for effective translation of genomic science into precision population health and medicine. Employing a community-based participatory mixed methods research design, we developed a semi-structured survey that was disseminated to three cancer advocacy organizations."
Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives.
Brandie Heald et al. J Natl Cancer Inst 2023 9
(Posted: Oct 02, 2023 11AM)
From the abstract: "Cascade testing using multigene panels was performed in 3,696 relatives of 7,433 probands. Unexpected PGVs were identified in 230 (6.2%) relatives, including 144 who were negative for the familial PGV but positive for a PGV in a different gene than the proband and 74 who tested positive for the familial PGV and had an additional PGV in a different gene than the proband. Of the relatives with unexpected PGVs, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial PGV would have resulted in missed, actionable findings for a subset of relatives."
Emerging cancer risks in BRCA2 pathogenic germline variant carriers.
Patrick R Benusiglio et al. Eur J Hum Genet 2023 9
(Posted: Sep 28, 2023 11AM)
From the paper: "Carriers of pathogenic germline variants (PGV) in BRCA2 could soon be offered gastric cancer screening using gastroscopy. In the longer term, some might even take part in lung cancer screening programs. Indeed, while the risks of breast, ovarian, pancreatic and prostate cancer have been documented for years, recent data show an increased risk of gastric cancer, and suggest an association with lung cancer. This article focuses specifically on BRCA2, while sidelining its sister gene BRCA1, as evidence for a broad cancer spectrum is much stronger for the former."
Risk perception and intended behavior change after uninformative genetic results for adult-onset hereditary conditions in unselected patients.
Nandana D Rao et al. Eur J Hum Genet 2023 9
(Posted: Sep 27, 2023 8AM)
From the abstract: "Overall, 2761 people received uninformative results and 1352 (49%) completed survey items. Respondents averaged 41 years old, 62% were female, and 56% were Non-Hispanic Asian. Results from the FACToR instrument showed mean (SD) scores of 0.92 (1.34), 7.63 (3.95), 1.65 (2.23), and 0.77 (1.50) for negative emotions, positive emotions, uncertainty, and privacy concerns, respectively, suggesting minimal psychosocial harms from genetic screening. Overall, 12.2% and 9.6% of survey respondents believed that their risk of cancer or heart disease, respectively, had changed after receiving their uninformative genetic screening results. Further, 8.5% of respondents planned to make healthcare changes and 9.1% other behavior changes. "
Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.
Burcu F Darst et al. JAMA Oncol 2023 9
(Posted: Sep 22, 2023 2PM)
From the abstract: " Do rare pathogenic variants in genes beyond previously established prostate cancer risk genes contribute to risk of aggressive prostate cancer? In this exome-sequencing genetic association study of 17?546 men with aggressive and nonaggressive prostate cancer, an association between known genes BRCA2, ATM, and NBN with aggressive prostate cancer was found. Nominal association evidence was observed for MSH2, XRCC2, and MRE11A. The findings of this study suggest that DNA repair and cancer susceptibility genes can inform disease management in men with nonaggressive prostate cancer, as men carrying deleterious variants in these genes are likely to develop advanced disease."
Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.
Silvia Actis et al. J Community Genet 2023 9
(Posted: Sep 21, 2023 2PM)
From the abstract: "We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. "
Biomarker-Directed Therapy in Black and White Men With Metastatic Castration-Resistant Prostate Cancer.
Clara Hwang et al. JAMA Netw Open 2023 9 (9) e2334208
(Posted: Sep 21, 2023 2PM)
From the abstract: "Do disparities exist in the application of precision medicine for Black and White men with metastatic prostate cancer?
In this cohort study of 962 men with metastatic castration-resistant prostate cancer, mismatch repair deficiency or microsatellite instability-high was significantly more frequent in Black men than White men. However, Black men were significantly less likely to receive molecularly matched targeted therapy than White men. These findings suggest that although precision medicine in metastatic prostate cancer has become more common, opportunities remain to improve access to precision medicine to benefit Black men with prostate cancer. "
Revolutionizing Cancer Research: The Impact of Artificial Intelligence in Digital Biobanking
C Frascarelli et al, J Per Med, September 2023
(Posted: Sep 18, 2023 11AM)
From the abstract: "As digital pathology and artificial intelligence (AI) have entered the precision medicine arena, biobanks are progressively transitioning from mere biorepositories to integrated computational databanks. Consequently, the application of AI and machine learning on these biobank datasets holds huge potential to profoundly impact cancer research. Methods. In this paper, we explore how AI and machine learning can respond to the digital evolution of biobanks with flexibility, solutions, and effective services. "
Do polygenic risk scores add to clinical data in predicting pancreatic cancer? a scoping review.
Louise Wang et al. Cancer Epidemiol Biomarkers Prev 2023 8
(Posted: Sep 16, 2023 1PM)
From the abstract: "21 studies examined associations between a PC-specific PRS and PC. Seven studies evaluated risk factors beyond age and sex. Three studies evaluated the change in discrimination associated with the addition of PRS to routine risk factors and reported improvements [(AUCs: 0.715 to 0.745; AUC 0.791 to 0.830; AUC from 0.694 to 0.711]. Limitations to clinical applicability included using source populations younger/healthier than those at risk for PC (n=10), exclusively of European ancestry (n=13), or controls without relevant exposures (n=1). While most studies of PC-specific PRS did not evaluate the independent discrimination of PRS for PC beyond routine risk factors, three that did showed improvements in discrimination. "
Systematic Evidence Review and Meta-Analysis of Outcomes associated with Cancer Genetic Counseling
JO Culver et al, Genetics in Medicine, September 6, 2023
(Posted: Sep 06, 2023 11AM)
From the abstract: "We conducted a systematic review and meta-analysis of 17 patient-reported and health services-related outcomes associated with pre- and post-test GC in GCRA in accordance with PRISMA guidelines and GRADE methodology. The true impact of GC on relevant outcomes is not known due to low quality or absent evidence. While a meta-analysis found that pre-test GC had beneficial effects on knowledge, worry and risk perception, the certainty of this evidence was low according to GRADE methodology. "
Precision medicine: biomarkers guide patient-specific treatment
Biotechniques, August 31, 2023
(Posted: Sep 01, 2023 7AM)
From the article: "Biomarkers are used to guide decision-making regarding the choice of therapy, predict treatment response, monitor treatment effectiveness and detect any recurrence or progression of the disease. Biomarkers in cancer treatment can be classified into several categories: diagnostic, prognostic, predictive and disease monitoring."
Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer
J Li et al, JAMA Network Open, August 30, 2023
(Posted: Aug 30, 2023 1PM)
From the abstract: " Is Ki-67 expression associated with the 21-gene recurrence score (RS) and with outcomes in patients with breast cancer with a low RS?
In this cohort study of 2295 patients with breast cancer, a moderate correlation was observed between Ki-67 and RS. Ki-67 had a significant association with disease recurrence beyond 3 years and with secondary endocrine resistance in patients with a low RS."
Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors
HS Iyer et al, JAMA Network Open, August 30, 2023
(Posted: Aug 30, 2023 1PM)
From the abstract: "What are the relative strengths of associations of African genetic ancestry and neighborhood social environment with outcomes in Black breast cancer survivors? In this cohort study with 1575 Black female breast cancer survivors aged 20 to 75 years at diagnosis, African genetic ancestry was more strongly associated with tumor subtype than mortality. Associations between neighborhood socioeconomic status and mortality were attenuated following adjustment for potential mediators, including individual socioeconomic factors, lifestyle factors, and comorbidities."
Refining a multifaceted model of perceived utility of genomic sequencing results.
Devan M Duenas et al. Public Health Genomics 2023 8
(Posted: Aug 25, 2023 9AM)
From the abstract: "Research on the perceived utility of genomic sequencing has focused primarily on pediatric populations and on individuals and families with rare genetic diseases. Here, we evaluate how well a multifaceted perceived utility model developed with these populations applies to a diverse, adult population aged 18-49 at risk for hereditary cancer and propose new considerations for the model. Participants’ discussions of utility often involved multiple domains and revealed the variety of ways in which receiving sequencing results can impact one’s life. Results demonstrated that an individual’s perception of utility can change over the life course when sequenced at a relatively young age and may be influenced by the resources available to them to act on the results."
Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians.
Hiroshi Y Yamada et al. NPJ Precis Oncol 2023 8 (1) 79
(Posted: Aug 21, 2023 8AM)
We compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1).
Headway against Brain Tumors with Molecular Targeting of IDH-Mutant Gliomas.
David Schiff et al. N Engl J Med 2023 8 (7) 653-654
(Posted: Aug 21, 2023 8AM)
Curious about your cancer risk, or if your child might develop learning disabilities? There’s a genetic test for that—but it may not be accurate
E Prater, Fortune Well, July 2023
(Posted: Aug 18, 2023 8AM)
A new wave of expanded genetics tests is flooding the market—social media feeds, at least—and complicating matters. Some promise to predict the gender of your baby, your child’s predisposition to learning disabilities, how specific medications might interact with your genetics, and even how prone you are to developing ear wax. Not all information provided by such tests is useful or accurate. And not all of the accurate information can be acted upon, experts caution. Often, disease can’t be prevented.
Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk
N Wilcox et al, Nat Genetics, August 17, 2023
(Posted: Aug 18, 2023 7AM)
To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P?<?2.5?×?10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1.
Metaplastic breast cancer and BRCA1: first strong evidence of a link
D Gareth et al, EJHG, August 17, 2023
(Posted: Aug 17, 2023 11AM)
An international multi-institutional validation study of the algorithm for prostate cancer detection and Gleason grading
Y Tolkach et al, NPJ Precision Oncology, August 15, 2023
(Posted: Aug 16, 2023 8AM)
Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection.
Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.
Matthew R Trendowski et al. Cancer Epidemiol Biomarkers Prev 2023 8
(Posted: Aug 15, 2023 2PM)
Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development. Methods: We used a previously published lung cancer PRS based on 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD, and the top five principal components for genetic ancestry.
AI-based skin cancer detection: the balance between access and overutilization
KP Venkatesh et al, NPJ Digital Medicine, August 15, 2023
(Posted: Aug 15, 2023 0PM)
A recent study evaluated the healthcare implications and costs of an AI-enabled mobile health app for skin cancer detection, involving 18,960 beneficiaries of a Netherlands insurer. They report a 32% increase in claims for premalignant and malignant skin lesions among app users, largely attributed to benign skin lesions and leading to higher annual costs for app users (€64.97) compared to controls (€43.09). Cost-effectiveness analysis showed a comparable cost to dermatologist-based diagnosis alone. This editorial emphasizes the balance in AI-based dermatology between increased access and increased false positives resulting in overutilization.
The Cancer Moonshot Immuno-Oncology Translational Network (IOTN) at age 5: Accelerating Cancer Immunotherapies.
Ananth Annapragada et al. J Natl Cancer Inst 2023 8
(Posted: Aug 14, 2023 1PM)
The IOTN is focused on accelerating translation of cancer immunology research from bench to bedside and improving immunotherapy outcomes across a wide array of cancers. The unique structure and team science approach of the IOTN is designed to accelerate discovery and evaluation of novel immune-based therapeutic and prevention strategies. We describe IOTN progress to date, including new initiatives and the development of a robust set of resources to advance cancer immunology research. We summarize new insights by IOTN researchers, some of which are ripe for translation for several types of cancers.
“I don’t need any more unknowns hanging over my head”: Cancer patients’ views on variants of uncertain significance and low/moderate risk results from genomic sequencing
S Shickh et al, Genet in Medicine, August 11, 2023
(Posted: Aug 11, 2023 11AM)
We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS). This was a qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Patients’ perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very “useful” and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary VUS results without clinical action perceived results as “concerning”, leading to harms such as hypervigilance about cancer symptoms.
Genetic Profiles Affect Smokers' Lung Cancer Risk
CN Martimez, Medscape, August 2023
(Posted: Aug 11, 2023 11AM)
Smokers with extreme phenotypes of high and low risk of developing tobacco-associated lung cancer have different genetic profiles, according to a multidisciplinary study conducted by specialists from the Cancer Center at the University of Navarra Clinic (CUN). The study was conducted using DNA from 133 heavy smokers who had not developed lung cancer at a mean age of 80 years, and from another 116 heavy smokers who had developed this type of cancer at a mean age of 50 years. This DNA was sequenced using next-generation techniques, and the results were analyzed using bioinformatics and artificial intelligence.
Machine learning for genetics-based classification and treatment response prediction in cancer of unknown primary.
Intae Moon et al. Nat Med 2023 8
(Posted: Aug 08, 2023 8PM)
Cancer of unknown primary (CUP) is a type of cancer that cannot be traced back to its primary site and accounts for 3–5% of all cancers. Established targeted therapies are lacking for CUP, leading to generally poor outcomes. We developed OncoNPC, a machine-learning classifier trained on targeted next-generation sequencing (NGS) data from 36,445 tumors across 22 cancer types from three institutions. Oncology NGS-based primary cancer-type classifier (OncoNPC) achieved a weighted F1 score of 0.942 for high confidence predictions (=0.9 ) on held-out tumor samples, which made up 65.2% of all the held-out samples
The Inflammatory Profile Correlates with COVID-19 Severity and Mortality in Cancer Patients
CE Budin et al, JPM, August 7, 2023
(Posted: Aug 08, 2023 8PM)
The correlation of the inflammatory profile with the severity of the disease in neoplastic patients with SARS-CoV-2 infection was addressed. A database of 1537 patients hospitalized in the pneumology department was analyzed. After applying the inclusion and exclusion criteria, 83 patients (67% males, 33% females) were included. Most of the analyzed patients were hospitalized with a moderate form of disease, explaining the significant percentage of 25% mortality. The frequency of the type of neoplasm was higher for lung cancer, followed by malignant colon tumor. We identified a significant association between the increased value of ferritin (p < 0.0001, OR = 22.31), fibrinogen (p = 0.009, OR = 13.41), and C-reactive protein (p = 0.01, OR = 7.65), respectively, and the level of severity of COVID-19.
Rebooting cancer screening with artificial intelligence
S Adams et al, Lancet, August 5, 2023
(Posted: Aug 07, 2023 10AM)
Cancer screening typically relies on a reductionist, all-comer population approach, with screening eligibility based predominantly on age. This approach does not account for the multidimensional complexity of each individual, including a person's biological, physiological, and environmental data, and can miss those who may be at high risk of disease. As the total number of cancer cases continues to increase, and at younger ages, a rebooting of cancer screening is needed.
BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype
H Fettle et al, ebiomedicine, August 5, 2023
(Posted: Aug 07, 2023 9AM)
Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. These data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected.
Somatic mutations in facial skin from countries of contrasting skin cancer risk.
Charlotte King et al. Nat Genet 2023 8
(Posted: Aug 04, 2023 10AM)
The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK, despite Singapore receiving 2–3 times more ultraviolet (UV) radiation. Aging skin contains somatic mutant clones from which such cancers develop. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection.
Testing your genes for cancer risk is way cheaper now — and it could save your life
NPR, August 2, 2023
(Posted: Aug 04, 2023 9AM)
Cancer is the second leading cause of death in the United States, and about 10% of it is thought to come from inherited genetic mutations that increase risk.
Experts say that millions of people in the U.S. are walking around with a genetic variant that raises their risk of developing cancer. The vast majority of them have no clue. That's a problem, because people who know they're at a higher risk for certain cancers can take action, like going for more frequent screening tests such as colonoscopies and mammograms or even having preventive surgeries.
