Category: 8. Health

  • The adverse effects of metabolic disorder on left ventricular myocardial mechano-energetic efficiency and dysfunction in ischemic cardiomyopathy: insight from a cardiac MRI study | Cardiovascular Diabetology

    The adverse effects of metabolic disorder on left ventricular myocardial mechano-energetic efficiency and dysfunction in ischemic cardiomyopathy: insight from a cardiac MRI study | Cardiovascular Diabetology

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  • Kolwicz SC Jr, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res. 2013;113(5):603–16.

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  • 3 Things You Should Know About Targeting NRG1 and Rare Drivers in Pancreatic Cancer

    3 Things You Should Know About Targeting NRG1 and Rare Drivers in Pancreatic Cancer

    RELEASE DATE: June 1, 2025
    EXPIRATION DATE: June 1, 2026

    LEARNING OBJECTIVES

    Upon successful completion of this activity, you should be better prepared to:

    • Evaluate the role of mutations in NRG1 and other genetic alterations in diagnosis and management.

    • Discuss current guidelines and treatment recommendations for the management of patients with advanced pancreatic cancer.

    • Analyze clinical trial data to inform the selection of emerging therapeutic agents for advanced pancreatic cancer.

    • Apply strategies to optimize molecular testing algorithms using diverse testing modalities in advanced pancreatic cancer.

    Accreditation/Credit Designation

    Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Acknowledgment of commercial support

    This activity is supported by an educational grant from Partner Therapeutics, Inc.

    Off-label disclosure/disclaimer

    This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity.

    Instructions for participation/how to receive credit

    1. Read this activity in its entirety.

    2. Go to https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref to access and complete the posttest.

    3. Answer the evaluation questions.

    4. Request credit using the drop-down menu.

    YOU MAY IMMEDIATELY DOWNLOAD YOUR CERTIFICATE.

    To date, 32 genes have been identified as frequently mutated in pancreatic ductal adenocarcinoma (PDAC).1 However, less than 10% of patients are eligible for an FDA-approved targeted therapy, highlighting the need for the development of novel therapeutics.2 Here are 3 things you should know about molecular testing and personalized strategies in pancreatic cancer.

    1 RNA testing is critical to identify actionable gene fusions in PDAC.

    NCCN guidelines recommend tumor molecular profiling in cases of metastatic PDAC.3 RNA-based next-generation sequencing (NGS) is preferred to DNA-based NGS for detecting fusions in genes like ALK, NRG1, NTRK, ROS1, FGFR2, and RET. These fusions are enriched in the 5% to 10% of patients with KRAS wild-type PDAC, a molecular profile more often found in patients younger than 50 years.4 NGS using tumor tissue is preferred to blood-based assays, according to NCCN guidelines.3 Liquid biopsy can be performed concurrently with tissue testing or used when adequate tissue is unavailable.

    RNA-based NGS can detect structural variants of gene fusions, which may inform the potential efficacy of targeted therapies.5 Since RNA sequencing encompasses only exons after splicing, this technique can overcome the technical challenges of excessive sequencing or misaligned reads when DNA-based NGS is used on genes with long or repetitive introns (Figure 1).6 In a heterogeneous tumor in which the gene fusion is present only in some cells, RNA-based NGS can detect the alteration if it is highly expressed.

    FIGURE 1.RNA-based NGS May Overcome Limitations of DNA-Based Testing6

    2 The first NRG1-targeted therapy is approved for advanced or metastatic PDAC.

    NRG1 fusions are found in approximately 1% of solid tumors, most commonly in patients with mucinous adenocarcinoma of the lung and KRAS wild-type PDAC.7 These altered proteins consist of the EGF-like domain of NRG1 attached to the transmembrane domain of various fusion partners. This construct enables constitutive binding and activation of the HER3 receptor, activating RAS and the MAPK and PI3K signaling pathways.

    Zenocutuzumab is a HER2×HER3 bispecific antibody that inhibits NRG1 binding.8 In the phase 1/2 eNRGy trial (NCT02912949), zenocutuzumab demonstrated an overall response rate (ORR) of 30% (95% CI, 23%-37%) in 158 patients of all tumor types with NRG1 fusions.9 The response rate in 33 patients with PDAC was 42.4% (95% CI, 25.5%-60.8%), including 1 complete response and 13 partial responses (Figure 2).10 The median progression-free survival in the overall population was 6.8 months (95% CI, 5.5-9.1 months).9 The most common treatment-related adverse events (TRAEs) were diarrhea (18%), fatigue (12%), and nausea (11%). Infusion-related reactions occurred in 14% of patients. Based on results from the eNRGy study, zenocutuzumab received accelerated approval from the FDA as a second-line systemic therapy to treat advanced, unresectable, or metastatic PDAC harboring an NRG1 gene fusion.11

    FIGURE 2. Response to an NRG1 Inhibitor in Pancreatic Adenocarcinoma10

    3 Ongoing investigations are evaluating numerous other emerging targets of interest.

    In addition to NRG1 fusions, 38.5% of KRAS wild-type PDAC tumors harbor other genetic alterations, including FGFR2 or FGFR3 fusions, ERBB2 (HER2) amplification, BRAF mutations, and RET fusions.4 Erdafitinib demonstrated an ORR of 30% (95% CI, 24%-36%) in patients of different tumor types harboring FGFR alterations in the single-arm, phase 2 RAGNAR trial (NCT04083976).12 The ORR was 56% in patients with PDAC.

    Combination dabrafenib and trametinib produced an ORR of 38% (95% CI, 22.9%-54.9%) in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAF V600 mutation in the single-arm NCI-MATCH trial subprotocol H (NCT02465060).13 Of the 27 evaluable patients, the 1 patient with PDAC achieved stable disease. Combined use of dabrafenib and trametinib received accelerated approval to treat patients with unresectable or metastatic solid tumors, including PDAC, that harbor BRAF V600E mutations and who have progressed following prior treatment.14

    Selpercatinib yielded an ORR of 43.9% (95% CI, 28.5%-60.3%) in patients with RET fusion-positive non-lung and non-thyroid solid tumors in the phase 1/2 LIBRETTO-001 basket trial (NCT03157128).15 The ORR was 44% in patients with PDAC. Selpercatinib received accelerated approval to treat adults with locally advanced or metastatic solid tumors, including PDAC, that harbor a RET gene fusion and who have progressed following prior treatment.16

    The HER2-targeting antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (T-DXd) has not provided as much benefit in patients with PDAC. In the phase 2 DESTINY-PanTumor02 trial (NCT04482309) in patients with solid tumors overexpressing HER2 (immunohistochemistry [IHC], 3+ or 2+), the ORR was 37.1% (95% CI, 31.3%-43.2%) across all cohorts, but only 4.0% (95% CI, 0.1%-20.4%) in those with PDAC.17 Further investigation would be required to determine why this disease type is particularly resistant to T-DXd, but this agent is still approved for HER2 IHC 3+ PDAC under the tissue agnostic approval.

    The TP53 Y220C mutation is the target of the first-in-class p53 reactivator PC14586.18 In the phase 1 portion of the phase 1/2 PYNNACLE trial (NCT04585750) at the highest dose of PC14586, the ORR was 46.2%. In 6 patients with PDAC, 4 achieved stable disease, and 1 achieved an unconfirmed partial response.

    Claudin18.2 (CLDN18.2) is an emerging actionable target in many cancers, including PDAC.19 Therapeutics with various mechanisms of action are under investigation to exploit this target. IBI389 is a CLDN18.2×CD3 bispecific antibody evaluated in a phase 1 study (NCT05164458) in 64 previously-treated patients with CLDN18.2-positive PDAC.20 The ORR was 30.4% (95% CI, 13.2%-52.9%), and the disease control rate was 69.6% (95% CI, 47.1%-86.8%). TRAEs of grade 3 or greater were reported in 54.7% of patients. Treatment was discontinued in 4.7% of patients due to TRAEs. Cytokine release syndrome is an AE of particular concern with IBI389, with grade 1 or 2 events occurring in 51.6% of patients.

    Zolbetuximab is an anti-CLDN18.2 monoclonal antibody being tested against several tumor types and will be assessed in combination with gemcitabine/nab-paclitaxel (GN) vs GN alone as first-line therapy in patients with metastatic pancreatic cancer in a phase 2 study (NCT03816163).21 The primary end point is overall survival.

    Key References

    4. Singhi AD, George B, Greenbowe JR, et al. Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers. Gastroenterol. 2019;156(8):2242-2253.e4. doi:10.1053/j.gastro.2019.02.037

    6. Davies KD, Aisner DL. Wake up and smell the fusions: single-modality molecular testing misses drivers. Clin Cancer Res. 2019;25(15):4586-4588. doi:10.1158/1078-0432.Ccr-19-1361

    9. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N Engl J Med. 2025;392(6):566-576. doi:10.1056/NEJMoa2405008

    For FULL References List, visit https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref

    CME Posttest Questions

    1 A patient is referred to you with a new diagnosis of metastatic
    pancreatic ductal adenocarcinoma (PDAC) with multiple liver
    metastases. The patient is asymptomatic and has an ECOG perform-
    ance status of 0. Which of the following would be the next best step?

    A. Germline testing for inheritable pathogenic mutations

    B. Germline testing and somatic tissue testing

    C. Somatic tissue testing only

    D. Initiate systemic treatment without further testing

    2 Blockade of which of the following molecules is an active
    treatment approach in tumors with NRG1 fusions?

    A. EGFR

    B. HER3

    C. HER4

    D. NRG1

    3 A patient with metastatic PDAC is referred to you after disease
    progression on FOLFIRINOX. No somatic testing was performed at the time of diagnosis. On further investigation, the tumor has no evidence
    of KRAS mutations but has an ATP1B1-NRG1 fusion. Which of the following therapies would you choose at this time?

    A. Gemcitabine plus nab-paclitaxel

    B. Zenocutuzumab

    C. Zenocutuzumab plus gemcitabine

    D. Clinical trial of an NRG1 antibody

    Claim Your CME Credit at

    https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref

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  • Current Situation: Bird Flu in Dairy Cows | The Transmission

    Current Situation: Bird Flu in Dairy Cows | The Transmission

    CDC On April 1, CDC confirmed one human HPAI A(H5N1) infection in a person with exposure to dairy cows in Texas that were presumed to be infected with the virus. This is thought to be the first instance of likely mammal to human spread of HPAI A(H5N1) virus. In May 2024, CDC began reporting additional, sporadic human cases in people who had exposure to infected dairy cows. That latest human case counts are available at H5N1 Bird Flu: Current Situation Summary.

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  • Scientists reveal how chemotherapy causes genetic damage in healthy blood

    Scientists reveal how chemotherapy causes genetic damage in healthy blood

    For the first time, scientists have systematically studied the genetic effects of chemotherapy on healthy tissues.

    Researchers from the Wellcome Sanger Institute, the University of Cambridge, Cambridge University Hospitals NHS Foundation Trust (CUH) and their collaborators analysed blood cell genomes from 23 patients of all ages who had been treated with a range of chemotherapies.

    Published today (1 July) in Nature Genetics, the researchers show that many but not all chemotherapy agents cause mutations and premature aging in healthy blood.

    As part of Cancer Grand Challenges team Mutographs, the researchers uncovered new patterns of DNA damage, or mutational signatures, associated with specific chemotherapy drugs.

    The researchers suggest that the damaging genetic effects of chemotherapy identified by whole genome sequencing could guide the future treatment of patients with effective chemotherapies that have less harmful effects on healthy tissues.

    Chemotherapy is a type of anti-cancer treatment that works by killing cancer cells. It is a systemic treatment, meaning it works throughout the body, and can be administered as a single chemotherapy drug or a combination of drugs.1 In developed countries, it is estimated that around 10 per cent of the population has received chemotherapy treatments for cancer and other diseases at some point in their lifetime.2

    Chemotherapy can have long-term side effects on healthy, non-cancerous tissues, and is associated with an increased risk of secondary cancers. However, there is limited understanding of the biological mechanisms underlying these side effects.

    With new genomic technologies, researchers can explore mutations in normal cells and begin to investigate the extent and long-term consequences of DNA damage from chemotherapy on healthy tissues.

    In a new study, scientists set out to research the effects of chemotherapy on healthy blood. The Mutographs team at the Sanger Institute, University of Cambridge, CUH and their collaborators chose to study blood due to its ease in sampling and ability to culture blood in the laboratory. Plus, the numbers of mutations in normal blood are very consistent between people, giving a good baseline to see whether they are higher in individuals who have received chemotherapy.

    The researchers sequenced blood cell genomes from 23 individuals aged three to 80 years, who had been treated with a range of chemotherapies for various blood and solid cancers. Most of the patients were treated at Addenbrooke’s Hospital in Cambridge and had received a combination of chemotherapy drugs. Collectively, they had been exposed to 21 drugs from all of the main chemotherapy classes, including alkylating agents, platinum agents and anti-metabolites. The results were compared with genomic data from nine healthy people who had never received chemotherapy.

    From analysing the whole genome sequence data, the team found that many classes of chemotherapeutics, but not all, do produce higher numbers of mutations in normal blood cells. For example, a three-year-old patient who was treated for neuroblastoma, a cancer of nerve tissue, had more than the number of mutations found in 80-year-olds who had never received chemotherapy.

    By looking at patterns of damage in the DNA, known as mutational signatures, the researchers showed that different chemotherapeutics have different mutational signatures, and identified four new signatures found in chemotherapy-treated patients.

    For instance, the researchers found that some platinum agents, such as carboplatin and cisplatin, caused very high numbers of mutations. Whereas other drugs in the same class, such as oxaliplatin, did not.

    The researchers suggest that if these drugs are used interchangeably in cancer treatment, and assuming they have the same effectiveness, then this sort of genetic information could be incorporated in order to administer chemotherapies with fewer harmful effects.

    The team also made discoveries around the effects of chemotherapy on the population of cells that generate blood, known as hematopoietic stem cells.

    In normal aging, the hematopoietic stem cells producing blood decrease in diversity, due to the expansion of clones of cells that have “driver” mutations in cancer genes. Chemotherapy caused a similar pattern of change, but prematurely in some middle-aged adults. Particularly in children who have had chemotherapy, their blood appeared to prematurely age, which may increase the risk of secondary cancer later in life.

    Scientists suggest that genomic data could help in choosing the chemotherapies for children that minimise this premature aging, and genomic technologies could monitor for further changes later in life.

    Dr Emily Mitchell, first author at the Wellcome Sanger Institute and clinician at CUH, said: “For the first time, we have taken a systematic view of the genetic effects of chemotherapy on healthy tissues – in this case, blood. We find that some, but not all chemotherapies cause genetic mutations and premature aging in normal blood. This study lays the groundwork for future research into the effects of chemotherapy on many other normal tissues, including multiple tissue sampling pre and post treatment, across a range of chemotherapies in a larger group of patients. This comprehensive view would reveal the full range of effects of different chemotherapies, and help us to optimise patient health in the long term.”

    Dr Jyoti Nangalia, co-lead author at the Wellcome Sanger Institute and Consultant Haematologist at CUH, said: “The effects of chemotherapy we see here – increasing numbers of mutations and premature aging of healthy blood – reasonably contribute to the heightened risk of additional cancers and the patient’s ability to tolerate further treatments in the future. Given that for many cancers, chemotherapy drugs can be switched with other agents to achieve similar results, we hope such genomic data will guide the optimisation of future treatment plans to deliver effective chemotherapies with much fewer damaging side effects for patients.”

    This important research helps us better understand how some chemotherapy drugs can affect healthy cells as well as cancer cells. While many cancers can now be targeted using precision therapies, chemotherapy remains a key way to treat some cancers and saves many lives every year, so it’s vital that patients continue with the treatment recommended by their doctor. At the same time, studies like this are crucial for helping scientists improve cancer treatments in the future – making them not only more effective but also safer for people living with cancer.”


    David Scott, Director of Cancer Grand Challenges

    Professor Sir Mike Stratton, Mutographs team lead and co-lead author at the Wellcome Sanger Institute, said: “I believe that the results of this study hold implications for the way that chemotherapies are used to treat cancer patients. We are constantly on the lookout for better ways of giving therapy and minimising the side effects of toxic, systemic treatments. I’m hopeful that the genomic information from this and future studies will guide choices of chemotherapies, and their adoption in clinical practice.”

    Source:

    Wellcome Trust Sanger Institute

    Journal reference:

    Mitchell, E., et al. (2025). The long-term effects of chemotherapy on normal blood cells. Nature Genetics. doi.org/10.1038/s41588-025-02234-x.

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  • Change trackers: New consortium to catalog DNA mutations across human lifetime

    From the time we are conceived and through old age, genetic mutations accumulate in all our tissues, eluding the body’s typically efficient DNA repair machinery and potentially affecting our health and well-being.

    In a new project, a team of researchers from multiple institutions including Yale will catalog these changes, known as somatic mutations, more than two decades since scientists first logged snapshots of 3 billion DNA base pairs that make up the human DNA. The project will focus specifically on mutations across 19 tissue sites in 150 individuals without disease.

    The project, called the Somatic Mosaicism across Human Tissues (SMaHT) Network, and which will include more than 300 researchers, is described today in the journal Nature. 

    “We want to know how many mutations there are in as many tissues of the body we can to understand how our body changes over time,” said Flora Vaccarino, the Harris Professor at the Yale Child Study Center, professor of neuroscience at Yale School of Medicine, and co-corresponding author of the perspective paper.

    There is a general belief that people are born with an immutable set of DNA sequences inherited from their parents that dictate almost all aspects of their biology.  But even a few days after fertilization, cells of the embryo develop somatic mutations which can affect development. In the embryo, mutations of single nucleotides within a cell, known as SNVs (single nucleotide variants), occur at a rate of about one to five SNVs per cell division. These mutations slow after birth to two to 65 SNVs per year, depending on the tissue, and so steadily accumulate in our cells as we age. Larger structural DNA mutations are much less frequent but potentially could have a larger impact.

    (Intriguingly, there are 10 times fewer mutations in germ line cells, the reproductive cells in sexually reproducing organisms, than in other post-conception cells.)

    Most of these somatic mutations have little effect on our health — and some may even be advantageous. Other mutations, however, including those which occur in many forms of cancer, can be life-threatening. While cancer is the most well-known disease associated with somatic mutations, recent studies have linked these mutations to developmental syndromes, neurological diseases and inflammatory disorders.

    However, there is no largescale reference database for mutations in different tissue types in a large general population that is needed to begin understanding their impact on development, aging, and disease.

    For the new project, collaborators will seek to define the prevalence and types of somatic mutations in healthy individuals in order to better identify those which may cause harm.

    “Until we understand what is happening in healthy people, we can’t understand what is happening in disease,” Vaccarino said.

    Specifically, the research consortium will look at somatic mutations in multiple tissue types including in the skin, brain, skeleton, heart, lungs, and blood. Finding these mutations in human tissues, however, is challenging, researchers say.

    “Specific mutations can be present in very small numbers of cells or even single cells, and so detecting them is like looking for a needle in a haystack,” said Tim Coorens, co-lead and co-corresponding author from the Broad Institute of MIT and Harvard and currently a research group leader at the European Bioinformatics Institute in Cambridge, UK.

    To overcome these challenges, the consortium is developing and applying state-of-the-art technological advances including sequencing approaches with ultra-low error rates and sequencing the DNA of single cells. This will allow them to track mutations of single nucleotides within a single cell and, at the same time, to monitor RNA which carry out instructions encoded within the DNA.

    “It is like a super-personal genome overtime,” Vaccarino said.

    Eunjung Alice Lee, of Boston Children’s Hospital and the Broad Institute, and Ji Won Oh, of Yonsei University College of Medicine in Seoul, South Korea, are co-lead authors of the perspective paper.

    The SMaHT Network, which includes more than 300 researchers from more than 50 institutions across the United States, is supported by the National Institutes of Health’s Common Fund.

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  • Mpox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids | The Transmission

    Mpox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids | The Transmission

    Nature In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging. Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads. Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.

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  • Researchers Find Immune Pathway in Joint Tissue involved in Early Rheumatoid Arthritis

    Researchers Find Immune Pathway in Joint Tissue involved in Early Rheumatoid Arthritis

    A new study by scientists at the University of Colorado Anschutz Medical Campus reveals that joint tissue from patients with early-stage rheumatoid arthritis often have high levels of a protein called granzyme used by the immune system to attack pathogens.

    (more…)

  • New viruses identified in bats in China | The Transmission

    New viruses identified in bats in China | The Transmission

    Live Science Bats found near orchards harbor pathogens that could be passed to livestock or humans. Scientists in China have discovered a host of never-before-seen viruses in bats that live near humans. These viruses include two that are closely related to the deadly Nipah and Hendra viruses, which can cause severe brain inflammation and respiratory disease in humans.

    The work, published June 24 in the journal PLOS Pathogens, highlights the importance of keeping a close eye on bats and other animals that live near human populations, and avoiding contact with them as much as possible.

    Bats are natural reservoirs for many pathogens that can cause disease in humans, but the full extent of the bacteria, viruses and other potentially infectious agents they harbor is not known. Most previous studies have focused on bat feces rather than on internal organs, mainly because it is easier to collect. However, that tells us only about the viruses that make their way into feces.

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  • Many older adults take aspirin for heart disease prevention without doctor’s advice

    Many older adults take aspirin for heart disease prevention without doctor’s advice

    Around 1 in 6 older adults take aspirin as their primary method of preventing cardiovascular disease – despite stricter guidelines that no longer always call for it, a study finds. 

    Almost one-quarter of those aspirin users started taking the medication without a physician recommendation and 8% had not discussed their use with any health care provider. 

    The results, published in the Journal of the American College of Cardiology, come from a survey of more than 2,500 adults aged 50 to 80 conducted for the University of Michigan’s National Poll on Healthy Aging. The new paper builds on a previous poll report, with additional analysis. 

    “For some patients without a history of cardiovascular disease, the benefits of taking aspirin for primary prevention may be offset by an increased risk of bleeding, especially as patients get older,” said Jordan K. Schaefer, M.D., senior author and clinical associate professor of internal medicine-hematology at University of Michigan Medical School. 

    “It is even more concerning when patients are taking aspirin without consulting their physician. A provider can’t help a patient understand the risks and benefits of aspirin if they are left in the dark.” 

    In the past decade, guidelines for who should take aspirin for cardiovascular reasons have been revised to reduce the situations in which it’s recommended. The changes were informed by newer research that highlighted significant bleeding risk associated with using the medication for primary prevention – that is, by people with no history of heart attack or other heart disease. 

    The American College of Cardiology and the American Heart Association advise against routine primary prevention aspirin use after age 70. The U.S. Preventive Services Task Force also recommends not starting aspirin for primary prevention after 60 and potentially stopping around age 75. 

    While the vast majority of primary prevention users in the study believed that aspirin reduces their risk of heart attack, just 68% agreed that it increases the risk of bleeding. 

    Just over 80% of respondents said aspirin helped with general health, and 29% believed it reduced the risk of dementia. 

    It appears that older adults taking aspirin may anticipate benefits beyond reducing the risk of cardiovascular disease and may not fully understand the added risk of bleeding.” 


    Mark D. Edwards, M.D., first author and internal medicine resident at U-M Health

    The younger survey participants, between the ages of 50 and 69, were more than twice as likely to take aspirin for primary prevention compared to those aged 70 to 80 years. 

    Women and those with a household income $60,000 or greater were also more likely to be primary prevention users. 

    “Aspirin use is much more of a complex question than it once seemed, which is all the more reason why it is important to consult a heath care provider when considering use,” said Geoffrey Barnes, M.D., M.Sc., co-author and associate professor of internal medicine-cardiology at U-M Medical School. 

    “I would recommend that anyone over 40 years old talk to their provider about their risk for cardiovascular disease, with careful consideration of family and health histories.” 

    Source:

    Michigan Medicine – University of Michigan

    Journal reference:

    Edwards, M. D., et al. (2025). Patient Use and Perceptions of Primary Prevention Aspirin in the United States. Journal of the American College of Cardiology. doi.org/10.1016/j.jacc.2025.04.060.

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  • Study Links Specific Hormone Therapies to Breast Cancer Risk in Younger Women

    Study Links Specific Hormone Therapies to Breast Cancer Risk in Younger Women

    Study findings suggest a positive association between estrogen plus progestin hormone replacement therapy (EP-HRT) and increased risk of breast cancer in young adult women. The data, published in Lancet Oncology, may provide deeper insight into the potential risks of specific HRT types in pre- and postmenopausal women to better guide clinical decision-making.1

    HRT Hormone Therapy sign surrounded by plants and hormone therapy pills | Image Credit: © tilialucida – stock.adobe.com

    “Hormone therapy can greatly improve the quality of life for women experiencing severe menopausal symptoms or those who have had surgeries that affect their hormone levels,” Katie O’Brien, PhD, lead author of National Institutes of Health (NIH)’s National Institute of Environmental Health Sciences (NIEHS), said in an official NIH release. “Our study provides greater understanding of the risks associated with different types of hormone therapy, which we hope will help patients and their doctors develop more informed treatment plans.”2

    Hormone replacement therapy (HRT) is often used to ease the symptoms of menopause, such as hot flashes, vaginal dryness, and mood swings, that arise as estrogen levels naturally decline with age. It may also be recommended for individuals who have undergone a hysterectomy or oophorectomy. There are 2 main types of HRT: estrogen-only therapy (E-HRT), typically reserved for those who no longer have a uterus, and combined estrogen-progestin therapy (EP-HRT), which is used when the uterus is intact to help reduce the risk of endometrial cancer.2,3

    Studies confirm that estrogen plus progestin is a risk factor for breast cancer in postmenopausal women, but there are little data on the impact of these therapies in young women who may need HRT following gynecological surgery or for perimenopausal symptom relief. In a pooled cohort analysis, an international team of researchers at the NIH investigated the relationship between exogenous hormone therapy and the risk of young-onset breast cancer, drawing on data from 10 to 13 prospective cohort studies conducted across North America, Europe, Asia, and Australia. This large-scale analysis followed women up to age 55, focusing on the impact of hormone therapy (HT; used interchangeably with HRT) on breast cancer incidence in younger populations—a group for whom data has historically been limited.1,2

    A total of 459,476 women between the ages of 16 and 54 years (mean age 42.0 years) were included in the study. Over a median follow-up of 7.8 years, 2% of participants (n = 8455) were diagnosed with breast cancer before age 55. HT use was reported by 15% of participants, with the most common regimens being estrogen plus progestin therapy (6%) and unopposed estrogen (5%).1

    The researchers found no overall association between HT of any type and young-onset breast cancer (HR 0.96; 95% CI, 0.88–1.04). However, use of estrogen-only therapy was associated with a significantly lower risk (HR 0.86; 95% CI, 0.75–0.98), corresponding to a 0.5% absolute risk reduction by age 55.1

    In contrast, combined estrogen plus progestin therapy was associated with a modestly elevated risk of young-onset breast cancer (HR 1.10; 95% CI, 0.98–1.24), particularly with longer duration of use (>2 years; HR 1.18; 95% CI, 1.01–1.38). The association was strongest among women with intact uteri and ovaries (HR 1.15; 95% CI, 1.02–1.31).1

    The team also reported results from a subtype-specific analysis, which revealed that estrogen plus progestin therapy was more strongly associated with estrogen receptor–negative (HR 1.44; 95% CI, 1.11–1.88) and triple-negative breast cancer (HR 1.50; 95% CI, 1.02–2.20), suggesting potential biological differences in hormone sensitivity.1

    These findings offer new insight into the differential impact of hormone therapy formulations on breast cancer risk in younger women. The results align with existing data on hormone therapy and later-onset breast cancer while highlighting the importance of individualized risk assessment when considering hormone use before age 55.

    “These findings underscore the need for personalized medical advice when considering hormone therapy,” said Dale Sandler, PhD, NIEHS scientist and senior author, in an official NIH release. “Women and their health care providers should weigh the benefits of symptom relief against the potential risks associated with hormone therapy, especially EP-HT. For women with an intact uterus and ovaries, the increased risk of breast cancer with EP-HT should prompt careful deliberation.”2

    REFERENCES
    1. O’Brien K, House M, Goldberg M, et al. Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group. The Lancet Oncol. June 30, 2025. Doi: 10.1016/S1470-2045(25)00211-6
    2. Breast cancer risk in younger women may be influenced by hormone therapy. NIH. June 30, 2025. Accessed July 2, 2025. http://nih.gov/news-events/news-releases/breast-cancer-risk-younger-women-may-be-influenced-hormone-therapy
    3. Hormone therapy for menopause. American College of Obstetricians and Gynecologists. February 2024. Accessed July 2, 2025. https://www.acog.org/womens-health/faqs/hormone-therapy-for-menopause

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