JCO precision oncology最新文献

{"title":"<i>ALK</i>-Rearranged Non-Small Cell Lung Cancer Presenting as a Large Mediastinal Mass: A Case Report.","authors":"Urs M Weber, Lawrence Einhorn, Paul A Bunn","doi":"10.1200/PO-24-00536","DOIUrl":"https://doi.org/10.1200/PO-24-00536","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400536"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407982","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":"Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.","authors":"Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M McShane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty","doi":"10.1200/PO-24-00451","DOIUrl":"https://doi.org/10.1200/PO-24-00451","url":null,"abstract":"<p><strong>Purpose: </strong>Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.</p><p><strong>Methods: </strong>Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of <i>PTEN</i> mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the <i>PTEN</i> gene and retained expression of PTEN were included in subprotocol Z1H. Copanlisib was given intravenously over 1 hour at a dose of 60 mg on days 1, 8, and 15 in a 21-day-on and 7-day-off schedule in 28-day cycles. Patients continued treatment until disease progression or unacceptable toxicity.</p><p><strong>Results: </strong>Overall, 49 patients (20 patients in Z1G and 29 in Z1H) were included in the primary efficacy analyses. The objective response rates in both cohorts were 0% (Z1G; 90% CI, 0 to 13.9) and 3.4% (Z1H; 90% CI, 0.2 to 15.3), respectively. The median progression-free and overall survival durations were 1.8 months (90% CI, 1.4 to 3.9 months) and 13.7 months (90% CI, 6.8 to 18.3 months) for the Z1G cohort and 1.8 months (90% CI, 1.8 to 2.1 months) and 9.0 months (90% CI, 5.4 to 13.3 months) for the Z1H cohort, respectively.</p><p><strong>Conclusion: </strong>Our results do not support the antitumor activity of single-agent copanlisib in tumors with PTEN loss regardless of mutation or deletion status or <i>PTEN</i> deleterious mutations with PTEN expression.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400451"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364851","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":"Precision-Guided Durable Response From Venetoclax With Decitabine in a Patient With a Metastatic Refractory <i>IDH2</i>-Mutant Cholangiocarcinoma.","authors":"Eylül Özgü, Ünal Metin Tokat, Ashkan Adibi, Şevval Nur Bilgiç, Esranur Aydın, Onur Tutar, Mutlu Demiray","doi":"10.1200/PO-24-00652","DOIUrl":"https://doi.org/10.1200/PO-24-00652","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400652"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364853","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":"Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers.","authors":"Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo","doi":"10.1200/PO-24-00556","DOIUrl":"10.1200/PO-24-00556","url":null,"abstract":"<p><strong>Purpose: </strong>Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.</p><p><strong>Methods: </strong>Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added <i>TP53</i> and <i>MYOD1</i> mutations to the BC predictors. The Gene Enhanced 6 (GE6) model further included <i>NF1</i>, <i>MET</i>, <i>CDKN2A</i>, and <i>MYCN</i> mutations, selected through least absolute shrinkage and selection operator regression. Model performance was assessed using likelihood ratio tests and optimism-adjusted, bootstrapped validation and calibration metrics.</p><p><strong>Results: </strong>The GE6 model demonstrated superior predictive performance compared with the BC model (<i>P</i> < .001) and GE2 model (<i>P</i> < .001). The GE6 model achieved the highest discrimination with a time-dependent area under the receiver operating characteristic curve of 0.766. Mutations in <i>TP53</i>, <i>MYOD1</i>, <i>CDKN2A</i>, <i>MET</i>, and <i>MYCN</i> were associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative, <i>NF1</i>-positive disease was 50.0% (95% CI, 39 to 64) from BC but 76% (64 to 90) from GE6.</p><p><strong>Conclusion: </strong>Incorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared with traditional risk-classification schemas. Improved clinical variables and external validation are required before implementing these models into clinical practice.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400556"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364849","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":"Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.","authors":"Martina Haberecker, Jan H Rüschoff, Charitini Andriakopoulou, Steven G Gray, Kristiaan Nackaerts, Marc De Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Luca Ampollini, Joachim G Aerts, Michaela B Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P Finn, Enrico Silini, Jan Von Der Thüsen, Patrick Vagenknecht, Zoi Tsourti, Keith M Kerr, Roswitha Kammler, Solange Peters, Paul Baas, Isabelle Opitz, Rolf A Stahel, Alessandra Curioni-Fontecedro","doi":"10.1200/PO-24-00675","DOIUrl":"https://doi.org/10.1200/PO-24-00675","url":null,"abstract":"<p><strong>Purpose: </strong>CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data.</p><p><strong>Materials and methods: </strong>Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate <i>H</i>-score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome.</p><p><strong>Results: </strong>CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression (<i>H</i>-score ≥the median <i>H</i>-score of 120) was significantly more common in females (<i>P</i> = .0029; 71% <i>v</i> 47%) and in epithelioid histology (<i>P</i> < .001; 59% <i>v</i> 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank <i>P</i> = .043), but was not significant when adjusting for other clinical variables.</p><p><strong>Conclusion: </strong>Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400675"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408040","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":"Cancer Susceptibility Gene Testing in Patients With Pancreatic Ductal Adenocarcinoma: Implementation in a Cancer Center Oncology Clinic.","authors":"Hassan Sinan, Dea Cunningham, Emy Abou Sleiman, Dana Petry, Thomas McPhaul, Kala Visvanathan, Deborah K Armstrong, Jin He, Richard Burkhart, Michael J Pishvaian, Lei Zheng, Neeha Zaidi, Nilofer S Azad, Daniel Laheru, Michael Goggins","doi":"10.1200/PO-24-00494","DOIUrl":"10.1200/PO-24-00494","url":null,"abstract":"<p><strong>Purpose: </strong>Current guidelines recommend offering genetic susceptibility testing to individuals with pancreatic cancer regardless of family history, but previous studies have reported only moderate test uptake, highlighting the need for efficient and accessible clinical pathways for delivering pretest genetic education and testing. We evaluated gene testing uptake offered at the point-of-oncology care by a nongenetics provider in an outpatient setting.</p><p><strong>Methods: </strong>A retrospective chart review was performed of patients with pancreatic cancer treated at the Johns Hopkins Hospital between January 2021 and December 2023. During their initial clinic visit, patients were educated about germline testing by an oncology nurse and provided with educational and instructional handouts and video links, including how to arrange testing (with saliva) with a commercial testing provider. Patients with pathogenic variants and variants of uncertain significance were referred for genetic counseling.</p><p><strong>Results: </strong>Of the 992 patients seen in the oncology clinic (52.1% male, 75.4% White, 15.4% African American, 6% Asian; median age at diagnosis, 66.9 ± 10.6 years), 90% were offered testing, 77.6% of whom completed it. Factors significantly associated with not going forward with testing included being single, older age, African American, and having advanced-stage disease. Among the tested individuals, 78 (11.3%) had a pathogenic variant identified, including 55 (7.9%) with a pancreatic cancer susceptibility gene variant; of these, 72 (92.3%) were referred for genetic counseling and 50 (69.4%) completed their counseling visit. Testing led to a change in chemotherapy regimen in 28 patients.</p><p><strong>Conclusion: </strong>The implementation of point-of-care encounters for cancer susceptibility gene testing by an oncology nurse in the outpatient setting yielded a high uptake of testing. Additional approaches are needed to increase testing rates and cancer genetics visits.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400494"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407985","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":"Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy.","authors":"Jong Chul Park, Jong Seok Ahn, Ross Merkin, Manisha Patel, Lori Wirth, Thomas J Roberts","doi":"10.1200/PO-24-00741","DOIUrl":"https://doi.org/10.1200/PO-24-00741","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited.</p><p><strong>Methods: </strong>We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI. We extracted objective response rate (ORR), duration of treatment (DOT), and overall survival (OS) and compared them on the basis of patient characteristics. Multivariable models assessed associations between patient and tumor characteristics and outcomes.</p><p><strong>Results: </strong>We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC. Overall, the ORR was 21.4%, the median DOT was 1.9 months, and the median OS was 6.3 months. Patients receiving cetuximab with chemotherapy had a higher ORR (27.7% <i>v</i> 8.7%) and longer median DOT but similar OS compared with monotherapy. Virus-independent HNSCC had higher ORR (28.6% <i>v</i> 10.7%), longer DOT (3.3 <i>v</i> 1.2 months; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.90]), and longer OS (8.1 <i>v</i> 4.6 months; HR, 0.40 [95% CI, 0.19 to 0.83]). In multivariable models, virus-independent disease and negative smoking history were associated with improved OS. Concurrent chemotherapy, age, and sex were not associated with differences in OS. When assessing genomic data, <i>TP53</i> mutations were associated with improved DOT (HR, 0.33 [95% CI, 0.15 to 0.70]) and OS (HR, 0.38 [95% CI, 0.17 to 0.86]).</p><p><strong>Conclusion: </strong>Cetuximab-based therapy shows limited efficacy in R/M HNSCC post-ICI, although outcomes were better in virus-independent HNSCC and nonsmokers. The findings may improve prognostication and patient selection for cetuximab after ICI in R/M HNSCC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400741"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052678","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":"Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.","authors":"Leah H Biller, Kate Mittendorf, Miki Horiguchi, Alyson Caruso, Anu Chittenden, Chinedu Ukaegbu, Hajime Uno, Sapna Syngal, Matthew B Yurgelun","doi":"10.1200/PO-24-00691","DOIUrl":"10.1200/PO-24-00691","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical risk assessment models can identify patients with hereditary cancer susceptibility, but it is unknown how multigene cancer syndrome prediction models compare with syndrome-specific models in assessing risk for individual syndromes such as Lynch syndrome (LS). Our aim was to compare PREMMplus (a 19-gene cancer risk prediction model) with PREMM5 (a LS gene-specific model) for LS identification.</p><p><strong>Methods: </strong>We analyzed data from two cohorts of patients undergoing germline testing from a commercial laboratory (n = 12,020) and genetics clinic (n = 6,232) with personal and/or family histories of LS-associated cancer. Individual PREMMplus and PREMM5 scores were calculated for all patients. Using a score cutoff of <math><mrow><mo>≥</mo></mrow></math>2.5%, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for identifying LS with each model. Overall ability to discriminate LS carriers from noncarriers was measured using receiver operating characteristic (ROC)-AUC.</p><p><strong>Results: </strong>PREMMplus had higher sensitivity than PREMM5 in the laboratory- (63.7% [95% CI, 57.0 to 70.0] <i>v</i> 89.2% [95% CI, 84.4 to 93.0]) and clinic-based cohorts (60.8% [95% CI, 52.7 to 68.4] <i>v</i> 90.5% [95% CI, 84.8 to 94.6]). NPV was ≥98.8% for both models in both cohorts. PREMM5 had superior discriminatory capacity to PREMMplus in the laboratory- (ROC-AUC, 0.81 [95% CI, 0.77 to 0.84] <i>v</i> 0.71 [95% CI, 0.67 to 0.75]) and clinic-based cohorts (ROC-AUC, 0.79 [95% CI, 0.75 to 0.84] <i>v</i> 0.68 [95% CI, 0.64 to 0.73]).</p><p><strong>Conclusion: </strong>Both PREMM5 and PREMMplus demonstrated high NPVs (>98%) in LS discrimination across all patient cohorts, and both models may be used to identify individuals at risk of LS. The choice of which model to use can be based on the goals of risk assessment and patient population.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400691"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947928","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":"Association of Germline Pathogenic Variants in <i>MUTYH</i> and Other DNA Damage Response Genes With Lung Cancer Risk Among Non-Hispanic Whites and African Americans.","authors":"Matthew R Trendowski, Christine M Lusk, Angela S Wenzlaff, Christine Neslund-Dudas, Kristen S Purrington, Jennifer L Beebe-Dimmer, Ann G Schwartz","doi":"10.1200/PO-24-00558","DOIUrl":"10.1200/PO-24-00558","url":null,"abstract":"<p><strong>Purpose: </strong>Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).</p><p><strong>Materials and methods: </strong>Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race.</p><p><strong>Results: </strong>We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]). <i>MUTYH</i> variants were associated with lung cancer overall (OR, 1.82 [95% CI, 1.10 to 3.12]), with the strongest associations among never smokers (OR, 3.37 [95% CI, 1.08 to 10.26]), and in individuals who do not meet current USPSTF screening criteria (OR, 2.85 [95% CI, 1.20 to 7.53]).</p><p><strong>Conclusion: </strong>Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype. <i>MUTYH</i>, a gene historically associated with colorectal and other GI malignancies, emerged as a candidate gene that should be examined in individuals who do not have a significant smoking history.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400558"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033112","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":"Human Epidermal Growth Factor Receptor 2 Alterations and Prognostic Implications in All Subtypes of Breast Cancers.","authors":"Arielle L Heeke, Andrew Elliott, Kaitlyn O'Keefe, Chad Livasy, James T Symanowski, Meghan R Steiner, Irene M Kang, Dave S B Hoon, Philip Walker, George W Sledge, Milan Radovich, Paula R Pohlmann, Sandra M Swain, Antoinette R Tan","doi":"10.1200/PO.23.00719","DOIUrl":"https://doi.org/10.1200/PO.23.00719","url":null,"abstract":"<p><strong>Purpose: </strong>Alterations in human epidermal growth factor receptor 2 (HER2; <i>ERBB2</i> gene) may be clinically relevant when considering HER2-targeted therapies. We have characterized the breadth of <i>ERBB2</i> alterations (mutation, fusion, and copy number amplification) in breast cancer and explored the relationship between <i>ERBB2</i> alterations and prognosis.</p><p><strong>Methods: </strong>DNA next-generation sequencing (592-gene panel and whole-exome sequencing) and RNA whole-transcriptome sequencing data from 12,153 breast samples were retrospectively reviewed for <i>ERBB2</i> alterations. Clinicopathologic features were described, including breast cancer subtype, age, and biopsy site. HER2 status was determined according to ASCO guideline recommendations, including HER2-low. Overall survival (OS) data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for defined patient cohorts. Statistical significance was determined using chi-square and Wilcoxon rank-sum tests.</p><p><strong>Results: </strong>Pathogenic <i>ERBB2</i> mutations (<i>ERBB2-</i>mut) were identified in 3.2% (N = 388) of tumors overall, most common in liver metastases (113/1,972, 5.7%). <i>ERBB2-</i>mut was more common among breast lobular than ductal (10% <i>v</i> 2.1%; <i>P</i> < .001) and HER2-positive (HER2+)/low tumors (≥3.8% <i>v</i> 1.5% TNBC; <i>P</i> < .05). The most common variant was <i>ERBB2</i>-L755S (1.0% prevalence), enriched in metastatic tumors (1.2% <i>v</i> 0.6% in primary; <i>P</i> < .001). <i>ERBB2</i> fusions were rare (0.3% prevalence). Coalterations associated with <i>ERBB2</i>-mutated tumors compared with <i>ERBB2</i> wildtype (WT) included <i>CDH1</i> (40.0% <i>v</i> 10.2%; <i>P</i> < .001) and <i>ERBB3</i> (10.6% <i>v</i> 0.8%; <i>P</i> < .001). Of the 10,115 tumor samples with outcome data, <i>ERBB2-</i>mut was associated with worse OS compared with WT.</p><p><strong>Conclusion: </strong><i>ERBB2-</i>mut and fusions were observed in all breast cancer subtypes-more commonly in HER2+/low, metastatic, and lobular histology tumors-and associated with poorer prognosis.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2300719"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070895","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}