Hereditary Cancer in Clinical Practice最新文献

{"title":"Trends in the uptake of nipple sparing mastectomy in BRCA1/2, PALB2 and other pathogenic variant carriers undergoing risk reducing mastectomy.","authors":"Marya Alsuhaibani, Amel Melanson, Alex Viezel-Mathieu, Tassos Dionisopoulos, Mark Basik, Jean Francois Boileau, Karyne Martel, Sarkis Meterissian, Joshua Vorstenbosch, Victor Villareal-Corpuz, William D Foulkes, Ipshita Prakash, Stephanie M Wong","doi":"10.1186/s13053-026-00351-0","DOIUrl":"10.1186/s13053-026-00351-0","url":null,"abstract":"<p><strong>Introduction: </strong>Risk-reducing mastectomy (RRM) for germline pathogenic variant (GPVs) carriers were historically performed as total mastectomy (TM) or skin-sparing mastectomy (SSM), although nipple-sparing mastectomy (NSM) has recently emerged as an oncologically safe RRM option.</p><p><strong>Methods: </strong>This retrospective cohort study included all female patients with confirmed BRCA1, BRCA2, PALB2, or other high-penetrance GPVs at two academic institutions in Canada between 2003 and 2024. Temporal trends in NSM uptake were assessed using the Mantel-Haenszel test for trend and multivariable logistic regression.</p><p><strong>Results: </strong>After exclusions, 559 GPV carriers including 319 (57%) affected carriers and 240 (43%) unaffected carriers comprised the study cohort. The median age at RRM was 45 years old (range 22-76) and most were BRCA1 carriers (46.7%) or BRCA2 carriers (44.4%). Overall, 310 carriers (55.5%) underwent NSM, 174 (31.1%) underwent SSM, and 75 (13.4%) underwent TM. NSM uptake was highest among patients aged 40-49 years (56%) and lowest in those ≥ 60 years (42%, p = 0.03). Relative to unaffected carriers, affected carriers (47% vs. 66%, p < 0.001) and those with prior radiation were less likely to undergo NSM (34.3% vs. 62.7%, p < 0.001). A clear increase in NSM occurred over time, from 11.9% pre-2012 to 74.4% after 2022 (p < 0.001). Multivariable analysis adjusting for age, GPV, parity, menopausal status, and personal history of breast cancer identified normal BMI (OR 1.99, 95% CI 1.18-3.34), lack of radiation exposure (OR 3.03, 95% CI 1.76-5.23), and year of surgery as independent predictors of NSM receipt (OR 1.25, 95% CI 1.19-1.32).</p><p><strong>Conclusion: </strong>There has been a significant increase in NSM use among BRCA1/2, PALB2 and other GPV carriers over the last two decades.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"24 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and facilitators of adherence to cancer prevention in Lynch Syndrome: an integrative review.","authors":"Marjorie Matekwa, Margaret H White, Janet H Van Cleave, Veronica J Brady, Carina Katigbak","doi":"10.1186/s13053-026-00348-9","DOIUrl":"10.1186/s13053-026-00348-9","url":null,"abstract":"<p><strong>Background: </strong>Lynch Syndrome, the most common hereditary cancer syndrome affecting 1 in 279 Americans, relies on primary care providers to identify at-risk individuals and promote adherence to prevention strategies. However, adherence remains suboptimal. This review examines barriers and facilitators impacting adherence for individuals with Lynch Syndrome and their primary care providers.</p><p><strong>Methods: </strong>A systematic search of six electronic databases (Embase, PubMed, MEDLINE, Google Scholar, CINAHL, and Web of Science) was conducted for studies published between 2011 and 2024. Studies examining barriers or facilitators to cancer prevention among individuals with Lynch Syndrome or primary care providers were included. Methodological quality was assessed using the Joanna Briggs Institute criteria for qualitative studies.</p><p><strong>Results: </strong>Four studies met the inclusion criteria (sample sizes 13-60). Key barriers included limited provider and patient knowledge of Lynch Syndrome, psychological distress related to cancer risk, uncertainty surrounding follow-up protocols, and competing lifestyle priorities. Facilitators included strong wellness motivation, family support, and coordinated care pathways that support surveillance and preventive care.</p><p><strong>Conclusions: </strong>Adherence to cancer prevention in Lynch Syndrome is influenced by psychosocial factors and provider knowledge gaps. Addressing these barriers through targeted education and coordinated care models may improve adherence to prevention in this high-risk population.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The psychosocial impact of receiving a polygenic risk score informing risk of prostate cancer.","authors":"Matthew Hogben, Emma Hainsworth, Barbara Benton, Jana McHugh, Kathryn Myhill, Eva McGrowder, Reshma Rageevakumar, Denzil James, Sarah Benafif, Elizabeth C Page, Rosalind A Eeles, Emma Rowland, Elizabeth K Bancroft","doi":"10.1186/s13053-026-00347-w","DOIUrl":"10.1186/s13053-026-00347-w","url":null,"abstract":"<p><strong>Background: </strong>Use of polygenic risk scores (PRS) as a risk-stratification tool in cancer screening is an area of increasing interest. The BARCODE1 study is an observational prostate cancer screening study, investigating the use of PRS to risk-stratify people by risk of prostate cancer, with those identified as higher risk invited for prostate cancer screening. Participants of BARCODE1 were invited to take part in a psychosocial sub-study aiming to explore the effect of receiving a polygenic risk score on psychological health, family risk communication and impact on health behaviours.</p><p><strong>Methods: </strong>1300 participants of the BARCODE1 study were invited to complete questionnaires before and after receiving the results of their PRS. A sub-group were invited to participate in one-to-one in-depth semi-structured interviews, conducted in-person, by telephone or video-call. Interviews were audio recorded and transcribed verbatim. Data were analysed using Reflexive Thematic Analysis and the results are reported here.</p><p><strong>Results: </strong>Eighteen participants were interviewed and four themes identified; (a) mutual benefit, (b) emotional impact, (c) risk communication and (d) stoical attitudes to health. Participants reported minimal short-term impact on psychosocial health reported following receipt of a PRS. All participants communicated their genetic risk with their spouse/partner; however, some chose not to inform their children. Participants described themselves as having typical 'male' stoical responses to managing their health and that they did not feel the PRS results had an impact on their health behaviours.</p><p><strong>Conclusions: </strong>Providing an individualised PRS informing future risk of prostate cancer was well received. Overall, participants did not report being psychologically, socially or emotionally affected by receiving this genomic risk information. For those identified as being at higher risk it is important that there is access to healthcare professionals who are competent in discussing the meaning of the results.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03857477 , registered 26th Feb 2019.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRCAShare: a video-based message can increase sharing of familial genetic test results.","authors":"Katie Riefski, Amber Aeilts, Alexandra Spencer, Sue Friedman, Julia Cooper, Leigha Senter","doi":"10.1186/s13053-026-00344-z","DOIUrl":"10.1186/s13053-026-00344-z","url":null,"abstract":"<p><strong>Background: </strong>Genetic testing for known familial pathogenic or likely pathogenic germline variants in cancer susceptibility genes is central to identifying relatives at heightened risk for cancer. However, current data suggest that uptake of this practice referred to as \"cascade testing\" remains suboptimal. Research demonstrates that healthcare providers can alleviate barriers to cascade testing by providing informational resources to facilitate patient-mediated sharing of their genetic test results with their at-risk relatives.</p><p><strong>Methods: </strong>We recruited 103 individuals with a pathogenic or likely pathogenic variant in BRCA1or BRCA2 (BRCA1/2). Participants were randomized to receive a family communication guide with or without a 2-minute video (BRCAShare) that describes the concept of a relative's recent diagnosis of a harmful variant in BRCA1/2, meant to facilitate sharing of results with relatives. All participants were given surveys to assess reactions to and impact of BRCAShare across three domains: (1) participants' sharing of genetic information and intent to share genetic information; (2) perceived susceptibility to and seriousness of BRCA1/2 cancer related risks, benefits, or barriers to intrafamilial sharing of results and cascade testing; (3) the impact of family dynamic on sharing of genetic information.</p><p><strong>Results: </strong>The group given access to the BRCAShare video (guide + video) had significantly higher odds of reporting an intent to share and actual sharing with other family members compared to those who did not receive BRCAShare (guide only). Perceptions of cancer risk did not change significantly after viewing BRCAShare, however participants demonstrated strong understanding of risks and benefits of genetic testing at baseline. There was not a significant association between family dynamics and more intent to share.</p><p><strong>Conclusions: </strong>Our research suggests that this video message is a useful method for facilitating family sharing of BRCA1/2 results.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association analysis of germline variants in GEN1 with a susceptibility to prostate cancer in Polish men.","authors":"Katarzyna Gliniewicz, Klaudia Stempa, Dominika Wokołorczyk, Wojciech Kluźniak, Milena Kiljańczyk, Helena Rudnicka, Tomasz Huzarski, Jacek Gronwald, Jan Uciński, Tadeusz Dębniak, Marta Grabarczyk, Anna Jakubowska, Marek Szwiec, Marcin Lener, Jan Lubiński, Steven A Narod, Mohammad R Akbari, Cezary Cybulski","doi":"10.1186/s13053-026-00343-0","DOIUrl":"10.1186/s13053-026-00343-0","url":null,"abstract":"<p><strong>Background: </strong>The GEN1 gene is involved in DNA damage repair, as are several prostate cancer susceptibility genes, and is now included in several NGS clinical testing panels. The aim of our study was to investigate the role of GEN1 mutations in the etiology of prostate cancer.</p><p><strong>Methods: </strong>First, we sequenced GEN1 in 390 Polish men with familial prostate cancer and 300 population controls using exome sequencing to identify protein-truncating variants and to analyze their possible association with prostate cancer risk. In addition, we performed a large association study of a recurrent frameshift variant of GEN1 (c.1929_1932delAAAG) among 5,857 men with unselected prostate cancer and 3,956 controls. We compared the clinical characteristics of prostate tumors in carriers of c.1929_1932delAAAG and in non-carriers. We conducted loss of heterozygosity (LOH) analysis at the GEN1 locus in prostate cancers from two men with the c.1929_1932delAAAG variant. To analyze survival, patients were followed from diagnosis to death for an average of 101 months.</p><p><strong>Results: </strong>We detected two frameshift variants (c.2515_2519delAAGTT (p. Lys839Glufs*2), c.1539delT (p. Asp514Ilefs*13)) by sequencing the GEN1 gene of 390 Polish patients with familial prostate cancer and 300 cancer-free controls. Neither variant was associated with increased prostate cancer risk: c.2515_2519delAAGTT was detected in 20.5% of 390 cases and in 17.1% of 300 controls (p = 0.28), c.1539delT was detected in one case (0.3%) and none of the controls (p = 1.00). The GEN1 variant, c.1929_1932delAAAG (p. Lys645Cysfs*29), was observed in 13 of 5,857 (0.22%) unselected cases and 8 of 3,956 (0.20%) controls (OR = 1.10, p = 0.84). Clinical characteristics of prostate tumors in 13 carriers of c.1929_1932delAAAG and 5,844 non-carriers were similar. All-cause survival was similar for variant carriers and non-carriers (age-adjusted HR = 0.68, p = 0.76). The wild-type GEN1 allele was not lost in two prostate tumors in men with the c.1929_1932delAAAG variant.</p><p><strong>Conclusions: </strong>Our analysis suggests that GEN1 is not a prostate cancer susceptibility gene. The study has clinical implications for genetic counseling of men who tested positive for germline variants of GEN1.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are current Polish guidelines for prophylactic mastectomy sufficient?","authors":"Adam Stachowski, Cezary Cybulski, Jacek Gronwald, Tomasz Huzarski, Tadeusz Dębniak, Tomasz Byrski, Steven Narod, Rodney Scott, Jan Lubiński","doi":"10.1186/s13053-026-00338-x","DOIUrl":"10.1186/s13053-026-00338-x","url":null,"abstract":"<p><strong>Aim: </strong>Due to the expansion of knowledge about genetic predispositions to breast cancer, the International Hereditary Cancer Center in Szczecin has been solicited to update the Polish ministerial guidelines for the qualification of patients who should be offered prophylactic mastectomy.</p><p><strong>Methods: </strong>This publication is a review of the scientific literature on the impact of TP53, PTEN, PALB2, CHEK2 pathogenic variants (PVs) predisposing to breast cancer. The number of prophylactic procedures was estimated in May 2024 based on the analysis of pedigree, clinical data and a telephone survey of unselected carriers of the Cancer Genetics Outpatient Clinics in Szczecin.</p><p><strong>Results: </strong>The literature data justifies prophylactic mastectomy in all women who carry germline pathogenic variants in TP53, PTEN or PALB2. For CHEK2 carriers prophylactic mastectomy is only justified for women carrying a high-risk variant (i.e. carriers of protein-truncating variants with a positive breast cancer family history). We propose these changes will result in approximately 122 additional bilateral procedures and 25 unilateral procedures annually.</p><p><strong>Conclusions: </strong>Current, evidence based data supports extending the qualification criteria for prophylactic mastectomy among TP53, PTEN, PALB and CHEK2 PV carriers.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148165693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal cell carcinoma risk among individuals heterozygous for fumarate hydratase variants: further insights into genotype-phenotype correlations.","authors":"Trevor L Hoffman, Sony Wirio, Vivek Sethumadhavan","doi":"10.1186/s13053-026-00342-1","DOIUrl":"10.1186/s13053-026-00342-1","url":null,"abstract":"<p><strong>Background: </strong>FH-tumor predisposition syndrome (FH-TPS) is an autosomal dominant cancer predisposition syndrome caused by the fumarate hydratase (FH) gene. FH was initially shown to cause hereditary leiomyomatosis and renal cell cancer (HLRCC), historically called Reed syndrome. More recently, certain germline FH variants have been linked to pheochromocytoma (PHEO) risk in individuals without features of HLRCC. Diagnosis of these apparently non-overlapping conditions, FH-TPS-PHEO and FH-TPS-HLRCC, has increased through application of broad hereditary cancer gene panels. Early HLRCC studies suggested high lifetime RCC risk; however, emerging data suggests RCC risk in FH-TPS-HLRCC is lower than previous estimates.</p><p><strong>Methods: </strong>Individuals with likely pathogenic or pathogenic (LPV/PV) FH variants were identified in a large, ethnically diverse health system. Heterozygotes were classified as FH-TPS-PHEO, FH-TPS-HLRCC, or FH-ARC (autosomal recessive carrier for congenital fumarate hydratase deficiency without FH-TPS risk) based on variant phenotype-genotype prediction. Groups were evaluated for demographics, FH testing indications, FH-TPS-HLRCC related clinical features, and RCC. Cumulative RCC incidence was estimated via Aalen-Johansen estimator.</p><p><strong>Results: </strong>Among 279 individuals with LPV/PV in FH, 4 had FH-TPS-PHEO, 111 FH-TPS-HLRCC, and 164 FH-ARC. The FH-TPS-HLRCC and FH-ARC groups were approximately two-thirds female. FH-ARC was less ethnically diverse due to a common variant in Northern Europeans (c.1431_1433dup). One-third of FH-TPS-HLRCC individuals underwent testing for cancer-related indications unrelated to FH-TPS-HLRCC, and nearly 75% of these were women who had uterine leiomyomata suggestive of FH-TPS-HLRCC. One-quarter of FH-TPS-HLRCC individuals were diagnosed via cascade testing, 40% of whom had clinical features of FH-TPS-HLRCC. RCC occurred in nine patients (5 FH-TPS-HLRCC, 3 FH-ARC, 1 FH-TPS-PHEO). All RCCs in FH-TPS-HLRCC were FH-deficient and occurred at earlier average age than the sporadic RCC in other groups. Cumulative RCC incidence by age 70 was 7.3% (95% CI 2.1-15.3%) in FH-TPS-HLRCC and 2.6% (95% CI 0.0-7.1%) in FH-ARC. RCC risk before age 25 in FH-TPS-HLRCC was negligible.</p><p><strong>Conclusions: </strong>FH-TPS-HLRCC is underdiagnosed and RCC risk is lower than earlier HLRCC estimates. Many individuals are identified through broad hereditary cancer gene panel testing and exhibit less obvious manifestations such as uterine leiomyomata. Adult RCC surveillance is warranted in FH-TPS-HLRCC, but the need for pediatric screening merits further study.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast cancer specialists' experiences and attitudes towards mainstream genetic testing for patients with breast cancer.","authors":"Kirsten Allan, Linda Cicciarelli, Catherine Beard, Geoffrey J Lindeman, G Bruce Mann, Paul A James, Laura E Forrest","doi":"10.1186/s13053-026-00340-3","DOIUrl":"10.1186/s13053-026-00340-3","url":null,"abstract":"<p><p>BACKGROUND: Germline genetic testing is an increasingly important component of treatment decision-making for clinicians and patients with breast cancer. To address increased demand and expedite access to genetic testing for these patients, the Parkville Familial Cancer Centre (PFCC) in Victoria, Australia, implemented a breast mainstream genetic testing program. The program educates and supports breast cancer specialists to provide eligible patients with pre-test information, gain consent, and arrange genetic testing during their routine cancer appointments. This study aimed to explore breast cancer specialists’ experiences and opinions of the education program and of facilitating mainstream genetic testing for their patients. METHODS: Specialists who had attended the mainstream genetic testing education were invited to complete an online survey about the training provided through the education program and their experience of deploying mainstream genetic testing in their practice. Descriptive statistics were compiled, and content analysis used for open text responses. RESULTS: Forty-five breast cancer specialists (breast surgeons, medical oncologists, radiation oncologists and breast care nurses) responded (45% response rate). Most respondents had discussed (87%) and consented (80%) patients for mainstream genetic testing. Most specialists (81%) rated their confidence levels as high or very high for consenting patients to mainstream genetic testing. The majority (89%) indicated that they believed mainstream genetic testing should be part of their role and felt well supported by the PFCC (90%). CONCLUSION: Breast cancer specialists used the education they received in the mainstream education program and were supported to deliver mainstream breast cancer genetic testing to their patients. </p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring and treatment patterns of von Hippel-Lindau disease-associated central nervous system hemangioblastomas.","authors":"Eric Jonasch, Yan Song, Jonathan Freimark, Manasi Mohan, James Signorovitch, Murali Sundaram","doi":"10.1186/s13053-026-00337-y","DOIUrl":"10.1186/s13053-026-00337-y","url":null,"abstract":"<p><p>BACKGROUND: Patients with von Hippel-Lindau-associated central nervous system hemangioblastoma (VHL-CNS-Hb) have a large economic burden, but there is limited real-world evidence describing their clinical burden in the United States (US). This study compared treatment patterns and monitoring procedures between patients with VHL-CNS-Hb and matched controls in the US. METHODS: Patients with VHL-CNS-Hb and matched controls were identified from Optum’s de-identified Clinformatics® Data Mart Database. The index date was the date of first CNS-Hb diagnosis (VHL-CNS-Hb cohort) or the date of a random medical claim within the patient’s claims (control cohort). Treatment patterns were assessed in the VHL-CNS-Hb cohort using unadjusted incidence rates. Pain management drug use, disease monitoring procedures, and visits to medical specialists were compared between cohorts using unadjusted and adjusted generalized linear models. Clinical trial number: not applicable. RESULTS: The most common treatment observed in the VHL-CNS-Hb cohort (N = 220) was targeted therapy for renal cell carcinoma (2.34 treatment events per 10 person-years). Pain management drug use, monitoring, and specialist visits peaked during the first/second year post-index. Compared to controls (N = 1100), VHL-CNS-Hb patients had higher rates of pain management drug use (adjusted incidence rate ratio [IRR]: 1.96), monitoring procedures (adjusted IRR: 3.93), and specialist visits (adjusted IRRs: 2.49–25.44; all P ≤ 0.001). CONCLUSIONS: Patients with VHL-CNS-Hb had a substantial, long-term clinical burden that included treatment for multiple VHL manifestations—reflecting the multi-organ nature of the disease—frequent pain management drug use, and high levels of healthcare use for disease monitoring and specialist visits. </p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of germline MMR gene variants on immune checkpoint inhibitors response in patients with MSI-H/dMMR digestive cancers: a retrospective cohort analysis.","authors":"Antoine Dardenne, Camille Loisel, Anna Pellat, Alexandre Perrier, Julie Metras, Thomas Samaille, Yann Parc, Julie Leclerc, Romain Cohen, Thierry André","doi":"10.1186/s13053-026-00339-w","DOIUrl":"10.1186/s13053-026-00339-w","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed outcomes in microsatellite instability-high (MSI-H) deficient mismatch repair (dMMR) cancers. The influence of germline MMR gene variants on ICI remains unclear. In this single-center study, 93 patients with Lynch syndrome-associated MSI-H/dMMR digestive cancers received ICI monotherapy or combination therapy. Germline MMR variants were classified, and progression-free survival (PFS) was evaluated by gene and variant type. Most patients carried MLH1 or MSH2 variants. At 24 months, estimated PFS was 81.5% for MLH1, 67.2% for MSH2/EPCAM, and 78.6% for MSH6, with no PFS events in MLH1 promoter methylation or PMS2 subgroups. No statistically significant differences in PFS were observed between gene groups. Performance status ≥ 2 was the only factor associated with poorer PFS. Neither MMR gene type nor variant class significantly influenced ICI efficacy in Lynch syndrome-related MSI-H/dMMR digestive cancers, supporting the use of ICIs regardless of germline MMR genotype.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}