JCO precision oncology最新文献

{"title":"Noncontrast Magnetic Resonance Fingerprinting-Habitat Framework for Intratumoral Heterogeneity Decoding and Isocitrate Dehydrogenase Mutation Prediction in Diffuse Gliomas.","authors":"Dandan Song, Borui Li, Yan Liu, Peixu Guo, Yaqin Mi, Binju Yang, Haiyuan Qu, Yueluan Jiang, Yang Song, Chengxiu Zhang, Guang Yang, Guoguang Fan, Miao Chang","doi":"10.1200/PO-26-00243","DOIUrl":"https://doi.org/10.1200/PO-26-00243","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and validate a magnetic resonance fingerprinting (MRF)-based habitat imaging framework for noninvasively decoding intratumoral heterogeneity (ITH) and preoperatively predicting isocitrate dehydrogenase (IDH) mutation status in diffuse gliomas.</p><p><strong>Materials and methods: </strong>In this prospective study (January 2024-September 2025), 141 adults with diffuse gliomas (56 IDH-mutant, 85 IDH-wildtype) were enrolled. Tumors were segmented into three habitats via K-means clustering of coregistered MRF-derived T2 and free water maps. A habitat-based radiomic model for IDH status was developed in a training cohort (n = 98) and validated in an independent test cohort (n = 43). Its performance was compared against a conventional whole-tumor model using area under the curve (AUC) and net reclassification improvement (NRI). Pathophysiological validation was performed by correlating habitats with the Ki-67 proliferation index, dynamic contrast-enhanced magnetic resonance imaging (<i>K</i>^<i>trans</i>), and apparent diffusion coefficient (ADC). The prognostic value for progression-free survival (PFS) was also assessed.</p><p><strong>Results: </strong>The MRF-habitat model outperformed the whole-tumor model for IDH genotyping (test AUC, 0.819 <i>v</i> 0.758; NRI, 0.833, <i>P</i> = .003). It identified a prognostically significant subregion (Subregion1) where T2 uniformity was an independent predictor of PFS (hazard ratio: 0.008; <i>P</i> = .033). Subregion2, a hypoxic-angiogenic niche, correlated with Ki-67 and exhibited higher <i>K</i>^<i>trans</i> and lower ADC in IDH-wildtype tumors (both <i>P</i> < .05). Patients stratified as high-risk by the model had significantly shorter median PFS (5.8 months <i>v</i> not reached, <i>P</i> = .043).</p><p><strong>Conclusion: </strong>The MRF-based habitat framework noninvasively decodes ITH, improves preoperative IDH genotyping, and identifies pathophysiologically distinct subregions with prognostic relevance.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600243"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Melanoma and Pancreatic Cancer Phenotype of a Potential <i>CDKN2A</i> Founder Variant, I49T (c.146T>C; p.Ile49Thr), in Individuals of Predominantly Mexican Ancestry.","authors":"Daisy Hernandez, Ashlie Browning, Amber Gemmell, Karlena Lara-Otero, Mariana Niell-Swiller, Jacqueline Mersch, Kathryn A Mraz, Daniella Kamara, Amie Blanco, Yvonne Cardona, Emmeline Chang, Jacob G Comeaux, Julie O Culver, James M Ford, Natalia Gutierrez, Jenny Lester, Beth Y Karlan, Ming Li, Qi Nie, Jesus Resendiz, Maria L Wei, Charité N Ricker","doi":"10.1200/PO-26-00083","DOIUrl":"10.1200/PO-26-00083","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic/likely pathogenic variants (P/LPVs) in the <i>CDKN2A</i> gene cause an increased risk of melanoma (MEL) and pancreatic cancer (PANC). The <i>CDKN2A</i> variant I49T (c.146T>C), reported to be recurrent in Hispanics, has conflicting pathogenicity classifications at laboratories, affecting clinical care. Multiple genetics clinics collaborated to explore cancers associated with I49T.</p><p><strong>Methods: </strong>Institutional clinical databases were queried for the <i>CDKN2A</i> variants, I49T, known P/LPVs, and c.-2G>A (a benign variant [BV]), and history of PANC and MEL was abstracted. A combination of statistical tests was used to investigate cancer history associations.</p><p><strong>Results: </strong>Data on 203 individuals, with qualifying <i>CDKN2A</i> variants detected on multigene testing between 2012 and 2023, were analyzed (I49T, n = 101; known <i>CDKN2A</i> P/LPVs, n = 57; BV, n = 45). Those with I49T were 91% less likely to have MEL than known <i>CDKN2A</i> P/LPVs (odd ratio [OR] = 0.089 [95% CI, 0.031 to 0.025]; <i>P</i> < .001) and were also less likely to have PANC (OR = 0.45 [95% CI, 0.14 to 1.41]; <i>P</i> = .17). However, mean age at PANC diagnosis for I49T was 56.0 years, significantly younger than known <i>CDKN2A</i> P/LPVs (μ = 71.0 years; <i>P</i> = .026).</p><p><strong>Conclusion: </strong>In the largest I49T study to date to our knowledge, MEL was significantly less frequent compared with known <i>CDKN2A</i> P/LPVs. Although a nonsignificant trend was observed for less PANC in I49T than known P/LPVs, individuals with I49T presented with PANC at a significantly younger age than those with known <i>CDKN2A</i> P/LPVs. The presence of I49T in Hispanics of mostly Mexican ancestry supports that it is a founder variant, relevant to understanding cancer risk in a large proportion of Hispanics in the United States.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600083"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organoids Serve as Viable In Vitro Model for Functional Precision Medicine for Mesonephric-Like Adenocarcinoma of the Ovary.","authors":"David Holthaus, Huy Duc Le, Laura Matzner, Franziska Kellers, Christoph Rogmans, Vincent Winkler, Lorenz Bastian, Stephanie Fliedner, Jörg-Paul Weimer, Hauke Busch, Tim Mandelkow, Björn Konukiewitz, Nicolai Maass, Marion van Mackelenbergh, Ibrahim Alkatout, Dirk O Bauerschlag, Nina Hedemann","doi":"10.1200/PO-26-00661","DOIUrl":"10.1200/PO-26-00661","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600661"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Evaluation of Circulating Tumor DNA in Metastatic Hormone-Sensitive Prostate Cancer.","authors":"Charles B Nguyen, Irene Tsung, Jessica K Lee, Lincoln W Pasquina, Amy Kasputis, Jennie L Lovett, Ryon P Graf, Amber Redmond, Frank C Cackowski, Elisabeth I Heath, David C Smith, Joshi J Alumkal, Todd M Morgan, Zachery R Reichert","doi":"10.1200/PO-25-01218","DOIUrl":"10.1200/PO-25-01218","url":null,"abstract":"<p><strong>Purpose: </strong>There are few established prognostic biomarkers in metastatic hormone-sensitive prostate cancer (mHSPC). Disease volume and timing of metastases are prognostic and predictive factors but may be inadequate due to heterogeneity. Circulating tumor DNA (ctDNA) provides both circulating volume (tumor fraction [TF]) and genomic data. There are limited data on ctDNA in mHSPC.</p><p><strong>Methods: </strong>This was a multicenter, prospective study of ctDNA testing in mHSPC. Presented here are the results before androgen-deprivation therapy initiation. The primary objective was to evaluate the association between TF and overall survival (OS) and time to mCRPC (TTCRPC). Secondary analyses included evaluating outcomes in subgroups of interest and key genomic subtypes.</p><p><strong>Results: </strong>Between 2018 and 2024, 85 patients were enrolled, of whom 72 (25% Black) had evaluable baseline ctDNA samples and are included herein. Baseline TF was positive in 46 patients (64%). Compared with patients with negative ctDNA TF, most patients with positive ctDNA TF had de novo (87% <i>v</i> 39%, <i>P</i> < .001) and high-volume disease (80% <i>v</i> 46%, <i>P</i> = .01). At a median follow-up of 20.8 months, median OS was not reached (NR) with those with negative ctDNA TF and 33 months with positive ctDNA TF (hazard ratio [HR], 3.33 [95% CI, 1.1 to 9.9]; <i>P</i> = .03). However, a negative TF at baseline was associated with an undetectable 7-month prostate-specific antigen, a validated OS surrogate. Median TTCRPC was NR versus 13 months (HR, 3.43 [95% CI, 1.5 to 7.9]; <i>P</i> = .004). ctDNA TF was also potentially prognostic in high-volume disease and those who received doublet therapy.</p><p><strong>Conclusion: </strong>In this diverse cohort, a positive ctDNA TF at baseline was associated with worse outcomes in mHSPC and may potentially complement current further risk stratification tools.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2501218"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Association Between Up-Front Next-Generation Sequencing and Overall Survival in Advanced Non-Small Cell Lung Cancer in the United States.","authors":"Susan C Scott, Danny Nguyen, Beilei Cai, Magdaliz Gorritz, Nydia Caro, Marie Yasuda, Yifan Gu, Chi-Chang Chen, Vincent Pretre, Teddy R Saliba, Benjamin P Levy","doi":"10.1200/PO-26-00108","DOIUrl":"https://doi.org/10.1200/PO-26-00108","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical guidelines recommend next-generation sequencing (NGS) before initiation of first-line (1L) therapy as the standard of care for patients with advanced non-small cell lung cancer (aNSCLC). This study examined the impact of timing of molecular testing in relation to treatment initiation on overall survival (OS) to help inform clinical decision making for aNSCLC treatment.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed the Flatiron Health aNSCLC deidentified database from 2019 to 2021. Patients with aNSCLC and 1L systemic therapy were grouped into three cohorts based on timing of testing: (1) up-front NGS; (2) up-front non-NGS genomic testing; and (3) NGS after 1L therapy initiation. Kaplan-Meier analysis and Cox Proportional Hazards models were used to compare OS from the date of aNSCLC diagnosis between cohorts.</p><p><strong>Results: </strong>Overall, 13,139 patients with aNSCLC treated with systemic therapy were identified, including 6,210 patients with up-front tumor NGS, 2,697 patients with up-front non-NGS testing, and 2,824 patients with NGS after 1L initiation. A higher proportion of patients with up-front NGS received targeted therapy compared with patients with NGS after 1L initiation (22.6% <i>v</i> 14.8%, <i>P</i> < .0001). Median OS was significantly longer (20.9 months) with up-front NGS compared with up-front non-NGS (17.5 months) and NGS testing after 1L (18.2 months, <i>P</i> < .005). Multivariable analyses suggest that OS benefits associated with up-front NGS were primarily attributable to treatment.</p><p><strong>Conclusion: </strong>NGS testing before 1L therapy was observed to be associated with earlier use of targeted therapy and longer survival when compared with other testing strategies. Future studies are warranted given the rapidly evolving treatment landscape in aNSCLC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600108"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Oral Cancer From Precursor Lesions: Assessing Current Methods and Future Directions.","authors":"Michael E Troka, James C Gates","doi":"10.1200/PO-26-00107","DOIUrl":"https://doi.org/10.1200/PO-26-00107","url":null,"abstract":"<p><strong>Purpose: </strong>Oral potentially malignant disorders (OPMDs) pose a significant clinical challenge due to their potential to develop into oral squamous cell carcinoma, a prevalence of 4%-5% of the US population, and malignant transformation rates that approach 10%. Current methods to assess risk of OPMD progression to oral cancer are fraught with limitations and incompletely predict risk.</p><p><strong>Methods: </strong>We review existing diagnostic and prognostic tools for OPMDs, examining their validation evidence, performance characteristics, and clinical utility.</p><p><strong>Results: </strong>Although some tools provide rule-in or rule-out capabilities, each tool interrogates a single biological layer, and none provides comparable positive predictive value and negative predictive value in a single tool.</p><p><strong>Conclusion: </strong>A framework integrating multiomic data across multiple different biologic processes and time points inclusive of benign mimics is needed to better identify which lesions are true OPMDs, and which warrant escalation and intervention versus surveillance or de-escalation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600107"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy Study of Vemurafenib in Children With Recurrent or Progressive BRAF^V600E- or BRAF^InsT-Mutant Brain Tumors: PNOC002.","authors":"Theodore Nicolaides, Raoull Hoogendijk, Marie Jaeger-Krause, Girish Dhall, Stewart Goldman, Amar Gajjar, Lindsay Kilburn, Sarah Leary, Jane Minturn, Nicholas Whipple, Divya Ramakrishnan, Janel Long-Boyle, Mariam Aboian, Michael Prados, Annette M Molinaro, Sabine Mueller","doi":"10.1200/PO-26-00558","DOIUrl":"10.1200/PO-26-00558","url":null,"abstract":"<p><strong>Purpose: </strong>Pediatric gliomas constitute the most prevalent central nervous system tumors in children, and aberrations in BRAF signaling contribute to their pathogenesis by disrupting the MAPK pathway. Targeted inhibition of this pathway using agents such as vemurafenib may hold therapeutic promise.</p><p><strong>Patients and methods: </strong>PNOC002 was a multicenter trial conducted through the Pediatric Neuro-Oncology Consortium in patients younger than 25 years with recurrent or progressive BRAF^V600E-mutant brain tumors. This combined phase 0/1 study aimed to establish the recommended phase II dose (RP2D) and assess preliminary efficacy, including tumor growth trajectories and rebound (defined as ≥25% increase in lesion size within 6 months, usually within 3 months, of stopping therapy).</p><p><strong>Results: </strong>Thirty-patients (range, 3-23 years) were treated at the RP2D of 550 mg/m² twice a day: 22 low-grade glioma (LGG) and 8 high-grade glioma (HGG). PFS at 6 months (PFS6) for the entire cohort was 80% (95% CI, 67 to 96). In patients with LGG, PFS6 was higher at 86% (95% CI, 73 to 100), compared with 63% (95% CI, 37 to 100) in patients with HGG. The best responses were stable disease (13 patients) and partial responses (13 patients). Four patients experienced PD, with three patients in the HGG cohort. Responsiveness varied by lesion type, with cystic lesions showing a larger and longer-lasting decrease in tumor size than solid lesions. Of 13 patients with LGG who discontinued treatment and had follow-up imaging, 3 (23%) experienced rebound within 78-97 days. The most common grade 3 adverse event was maculopapular rash (57%).</p><p><strong>Conclusion: </strong>Vemurafenib showed efficacy in children with recurrent or progressive BRAF^V600E-mutant brain tumors with acceptable toxicity. However, the rebound rate of 23% warrants further investigation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600558"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Predictive Biomarkers for Chemoradiotherapy Response in Rectal Cancer.","authors":"Mee-Na Park, Junho Kang, Jeong-Woo Hwang, Hye Won Lee, Incheol Seo, Shin Kim, Sang Jun Byun, Woon Kyung Jeong, Seong Kyu Baek, Sung Uk Bae","doi":"10.1200/PO-26-00262","DOIUrl":"https://doi.org/10.1200/PO-26-00262","url":null,"abstract":"<p><strong>Purpose: </strong>Chemoradiotherapy (CRT) is a standard treatment for rectal cancer, yet patients show marked variability in response. Identifying reliable biomarkers that predict CRT response remains an unmet clinical need.</p><p><strong>Methods: </strong>Pretreatment biopsy samples from patients who received neoadjuvant CRT were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified between responders and nonresponders, followed by functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. To complement DEG-based results, gene-set enrichment analysis (GSEA) was performed to assess pathway activity across the ranked transcriptome and to prioritize biologically relevant pathways. Pathway-derived gene signatures were evaluated using receiver operating characteristic curves and validated in three independent data sets.</p><p><strong>Results: </strong>A total of 1,477 DEGs were detected, including 729 upregulated and 748 downregulated genes in responders. Functional enrichment analysis indicated immune activation and epithelial polarity in responders, whereas nonresponders showed enrichment of extracellular matrix organization, focal adhesion, and phosphoinositide 3-kinase-protein kinase B signaling. GSEA further identified four pathways associated with CRT response: antigen presentation, extracellular matrix-receptor interaction, focal adhesion, and drug metabolism. Among these, the antigen presentation pathway consistently predicted treatment response across data sets. Elastic net regression defined a six-gene signature (<i>KLRC1</i>, <i>CTSS</i>, <i>HLA-DMA</i>, <i>HLA-DQB1</i>, <i>HLA-DQB2</i>, and <i>CIITA</i>) with strong predictive performance, with area under the curve values ranging from 0.76 to 0.81.</p><p><strong>Conclusion: </strong>These genes participate in major histocompatibility complex class II antigen-processing and immune-regulatory pathways that enhance CD4 T-cell activation. Overall, the findings indicate that an immune-active, antigen presentation phenotype underlies radiosensitivity in rectal cancer and that the six-gene signature may serve as a biomarker to guide personalized treatment strategies.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600262"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Disease-Agnostic Genomic Liquid Biopsy in Complex Diagnoses: Real-Life Example of cfChIP-Seq in a Fever of Unknown Origin.","authors":"Orly Agmon Gutin, Jenia Gutin, Dania Jaber, Gabriella Snoyman, Bara Hmeidat, Ronen Sadeh, Benjamin Glaser, Nir Friedman","doi":"10.1200/PO-25-01235","DOIUrl":"10.1200/PO-25-01235","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501235"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-Reducing Interventions in Women With Pathogenic Variants in Breast Cancer Susceptibility Genes.","authors":"Emily M Russell, Sarah M Nielsen, Rachel E Ellsworth, Heidi Chwan Ko, Rebecca A Previs, Daniel E Pineda-Alvarez, Edward D Esplin, Kevin Hughes, Stacy W Gray, Nadine M Tung, Allison W Kurian","doi":"10.1200/PO-26-00373","DOIUrl":"10.1200/PO-26-00373","url":null,"abstract":"<p><strong>Purpose: </strong>Recommendations for clinical management of women with germline pathogenic variants (PVs) in breast cancer susceptibility genes vary by gene. The goal of this study was to examine the utilization of risk-reducing strategies and treatments in women with germline PVs in breast cancer susceptibility genes.</p><p><strong>Methods: </strong>This cross-sectional study identified women with a PV in at least one of 13 breast cancer susceptibility genes from germline panel testing at a single commercial laboratory between 2015 and 2023. Paired health care claims data for 12 months after genetic testing were evaluated to estimate the utilization of risk-reducing mastectomy and salpingo-oophorectomy, breast magnetic resonance imaging (MRI), and pancreatic screening (magnetic resonance cholangiopancreatography or endoscopic ultrasound) in these women. Multivariable logistic regression models were used to evaluate the association of clinicodemographic factors and genetic testing results with intervention utilization.</p><p><strong>Results: </strong>Of 3,959 women with a PV (2,088 cancer-free; 1,871 with primary breast cancer diagnosed ≤120 days before genetic testing), the average age at testing was 45 years, 67% were White, and 90% reported a family history of cancer. Breast MRI was used by 33% of cancer-free women and 31% of women with breast cancer after genetic testing; pancreatic screening occurred in <11% of the eligible population. Women with PVs in <i>BRCA1</i>/<i>2</i> versus other breast cancer susceptibility genes had higher odds of risk-reducing mastectomy (cancer-free: odds ratio 7.2 [95% CI, 3.5 to 14.5]; with cancer: 6.0 [95% CI, 4.2 to 8.5]) and salpingo-oophorectomy (cancer-free: 7.2 (95% CI, 4.6 to 11.3]; with cancer: 13.8 [95% CI, 9.7 to 19.7]).</p><p><strong>Conclusion: </strong>Utilization of risk-reducing surgery was highest in women with <i>BRCA1</i>/<i>2</i> PV. Pancreatic screening was low in all patients. Future studies are needed to examine the factors underlying these trends.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600373"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}