JCO precision oncology最新文献

{"title":"Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial.","authors":"Sun Young Rha, Yanqiao Zhang, Anneli Elme, Roberto Pazo Cid, Ahmet Alacacioglu, Dimitrios C Ziogas, Kohei Shitara, Anastasija Ranceva, Radim Nemecek, Armando Santoro, Carlos Alberto Calderon, Krittiya Korphaisarn, Tracy Davis, Anita Zahlten-Kuemeli, Christopher Conn, Mengyao Tan, Hayden Honeycutt, Zev A Wainberg","doi":"10.1200/PO-24-00710","DOIUrl":"10.1200/PO-24-00710","url":null,"abstract":"<p><strong>Purpose: </strong>Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.</p><p><strong>Methods: </strong>As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.gov identifier: NCT05052801) were centrally tested for FGFR2b protein overexpression by immunohistochemistry (IHC) and had evaluable results. FGFR2b positivity was defined as both any % tumor cells (TC) and ≥10% TC exhibiting moderate-to-strong (2+/3+) membranous FGFR2b staining. Prevalence was analyzed across patient and sample characteristics.</p><p><strong>Results: </strong>FGFR2b protein overexpression at any % and ≥10%, 2+/3+ TC positivity was 37.8% (1,428/3,782 [95% CI, 36.2 to 39.3]) and 16.2% (612/3,782 [95% CI, 15 to 17.4]), respectively. Of any %, 2+/3+ TC-positive tumors, 42.9% (612/1,428 [95% CI, 40.3 to 45.4]) were FGFR2b ≥10%, 2+/3+ TC positive. FGFR2b prevalence was not notably different within multiple patient and sample characteristics examined (age, sex, collection method [biopsy <i>v</i> resection], collection site, location of primary tumor, and geographic region).</p><p><strong>Conclusion: </strong>As of the data cutoff date, we report the largest prevalence assessment of FGFR2b protein overexpression in GC with more than one third (37.8%) of patients with GC exhibiting FGFR2b protein overexpression (any % TC, 2+/3+) by a validated IHC assay. Approximately 16% of patients had FGFR2b protein overexpression in ≥10% of TC. FGFR2b prevalence was similar across geographic regions and within defined patient and sample variables regardless of the level of expression.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400710"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033118","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":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection.","authors":"James Yu, Aiwu Ruth He, Mahmoud Ouf, Rutika Mehta, Daniel A Anaya, Jason Denbo, Catherine Bridges, Antony Tin, Vasily N Aushev, Charuta C Palsuledesai, Shruti Sharma, Adham Jurdi, Minetta C Liu, Richard D Kim","doi":"10.1200/PO-24-00443","DOIUrl":"10.1200/PO-24-00443","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess (1) the prognostic value of circulating tumor DNA (ctDNA) and (2) the ability of ctDNA to detect recurrence compared with standard surveillance in curatively resected early-stage biliary tract cancer (BTC).</p><p><strong>Methods: </strong>This retrospective, multicenter cohort study evaluated serial ctDNA testing for surveillance in patients with early-stage BTC after curative resection. We evaluated the relapse-free survival (RFS) by ctDNA positivity. The sensitivity of ctDNA in detecting a confirmed recurrence of BTC, defined as a biopsy-proven or true progression by radiographic tumor dynamics, was evaluated. The lead time was calculated from the first ctDNA detection to the confirmed recurrence.</p><p><strong>Results: </strong>A total of 56 patients with curatively resected stage I-III BTC were included in this study, with a median follow-up of 12.8 months from the date of surgery. ctDNA detection during the molecular residual disease window period (median RFS, 6.6 months <i>v</i> not reached; hazard ratio [HR], 26 [95% CI, 2.6 to 265]; <i>P</i> < .0001) and during the surveillance period (median RFS, 19.3 months <i>v</i> not reached; HR, 20 [95% CI, 2.6 to 153]; <i>P</i> < .0001) were associated with poorer RFS. Sixteen patients had confirmed recurrence. ctDNA identified recurrence in 93.8.% (15/16) of the recurred patients with an average lead time of 3.7 months. Carbohydrate antigen 19-9 levels did not show any significant correlation with RFS (HR, 1.17 [95% Cl, 0.24 to 5.71]; <i>P</i> = .844) in contrast to ctDNA.</p><p><strong>Conclusion: </strong>The findings from our real-world cohort study revealed the (1) promising value of ctDNA as a prognostic biomarker for relapse in curatively resected BTC and (2) potential early detectability of recurrence by ctDNA compared with standard surveillance.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400443"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948416","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":"Digital Pathology-Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer.","authors":"Felix Y Feng, Matthew R Smith, Fred Saad, Pooya Mobadersany, Shaozhou K Tian, Stephen S F Yip, Joel Greshock, Najat Khan, Margaret K Yu, Sharon McCarthy, Sabine D Brookman-May, Ariel B Bourla, Tamara Todorovic, Rikiya Yamashita, Huei-Chung Huang, Trevor J Royce, Timothy N Showalter, Jacqueline Griffin, Akinori Mitani, Andre Esteva, Eric J Small","doi":"10.1200/PO-24-00653","DOIUrl":"https://doi.org/10.1200/PO-24-00653","url":null,"abstract":"<p><strong>Purpose: </strong>The SPARTAN trial demonstrated that the addition of apalutamide to androgen deprivation therapy improves outcomes among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). We applied a previously reported digital histopathology-based multimodal artificial intelligence (MMAI) algorithm to estimate clinical outcomes in SPARTAN.</p><p><strong>Methods: </strong>Patients with available hematoxylin and eosin-stained slides from the primary tumor were included. Histopathology slides were digitized. MMAI scores ranging from 0 to 1 were generated from digital histopathology and baseline clinical parameters. Patients were categorized into MMAI non-high-risk and high-risk groups using previously validated cutoffs. Kaplan-Meier estimates were calculated for metastasis-free survival (MFS), second progression-free survival (PFS2), and overall survival (OS); comparisons were performed using Cox proportional hazards regression for treatment arms and MMAI risk. The interaction between treatment arm and risk group was evaluated using a Cox proportional hazards model.</p><p><strong>Results: </strong>The study included 420 evaluable patients after excluding those with missing clinical data or inadequate histopathology images. Of these, 63% (n = 266) were MMAI high risk and 37% (n = 154) were non-high risk. MMAI risk score was associated with shorter MFS (hazard ratio [HR], 1.72; <i>P</i> < .005), PFS2 (HR, 1.57; <i>P</i> < .005), and OS (HR, 1.41; <i>P</i> = .02). MMAI high-risk patients receiving apalutamide demonstrated significant improvement in MFS (HR, 0.19; <i>P</i> < .005), PFS2 (HR, 0.47; <i>P</i> < .005), and OS (HR, 0.6; <i>P</i> = .01). The interaction between MMAI risk score and treatment for MFS (<i>P</i> = .01) and PFS2 (<i>P</i> = .03) was significant, indicating greater benefit from apalutamide treatment in MMAI high-risk patients.</p><p><strong>Conclusion: </strong>MMAI is a prognostic marker in nmCRPC and may serve as a predictive biomarker with high-risk patients deriving the greatest benefit from treatment with apalutamide. These results represent the first extension of an MMAI classifier to patients with castration-resistant prostate cancer, warranting additional validation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400653"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070892","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":"Tailored Approaches in the Treatment of Patients With Colorectal Cancer Harboring Tropomyosin Receptor Kinase Fusion and Microsatellite Instability-High: A Case Report and Literature Review.","authors":"Samuel Kim, Malak Itani, Xiuli Liu, Lulu Sun, Kilannin Krysiak, Nicole Fox, Belal Firwana, Sameer Al Diffalha, Upender Manne, Andreas Seeber, Molly Karl, Michele Frank, Hannah Stubblefield, Katrina Pedersen, Kian-Huat Lim, Hassan Abushukair, Moh'd Khushman","doi":"10.1200/PO.24.00305","DOIUrl":"https://doi.org/10.1200/PO.24.00305","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400305"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070905","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":"Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway.","authors":"Carlo María Cicala, Judit Matito, María Quindos, David Gómez-Peregrina, Paula Romero-Lozano, Paula Fernández-Suárez, Claudia Valverde, Macarena González, Stefania Landolfi, Paula Pérez-Albert, Luis Gros, Ana Vivancos, César Serrano","doi":"10.1200/PO-24-00497","DOIUrl":"https://doi.org/10.1200/PO-24-00497","url":null,"abstract":"<p><strong>Purpose: </strong>Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options. Therefore, it is critical to identify novel actionable alterations in SDH-deficient GIST.</p><p><strong>Patients and methods: </strong>We performed a single-center, retrospective analysis of patients with SDH-deficient GIST together with next-generation sequencing (NGS) analysis from their respective tumor samples to identify mutations and copy number alterations and chromosomal alterations. NGS-tailored treatment was implemented whenever possible.</p><p><strong>Results: </strong>Seventeen tumor samples from 14 patients with SDH-deficient GIST underwent NGS. Mutational load was low, although three patients (21%) displayed molecular events in relapse samples leading to PI3K/mTOR pathway hyperactivation. mTOR inhibition with everolimus obtained a sustained tumor response in a heavily pretreated patient. Other alterations, largely present in late-stage patients, uncovered genes involved in cell cycle regulation, telomere maintenance, and DNA damage repair. Chromosomal arm-level alterations differed from the canonical cytogenetic progression in KIT/PDGFRA-mutant GIST.</p><p><strong>Conclusion: </strong>This molecular landscape of SDH-deficient GIST uncovers novel molecular alterations, mostly in relapse and/or previously pretreated patients. The identification of genetic events leading to PI3K/mTOR dysregulation together with the remarkable activity of everolimus in one patient showcases the clinical relevance of this pathway, validates the utility of NGS in this population, and poses everolimus as a novel therapeutic alternative. Several other alterations were found at the genetic and genomic levels, underscoring novel biological processes likely involved during tumor evolution.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400497"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949068","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":"Clinical Outcomes and Molecular Profiling of Pancreatic Acinar Cell Carcinoma: A Retrospective Study.","authors":"Cody Eslinger, Bobak Seddighzadeh, Claire Yee, Zaid Elsabbagh, Rish Pai, Chris Hartley, Jason Starr, Tanios Bekaii-Saab, Thorvardur R Halfdanarson, Mohamad Bassam Sonbol","doi":"10.1200/PO-24-00450","DOIUrl":"https://doi.org/10.1200/PO-24-00450","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic acinar cell carcinoma (PACC) is a rare and aggressive form of pancreatic cancer that originates in the acinar cells of the exocrine pancreas. In this study, we aimed to investigate the clinical and molecular characteristics of patients with PACC at our institution.</p><p><strong>Methods: </strong>This was a retrospective study of patients with PACC seen at Mayo Clinic between 2002 and 2023. Baseline patient characteristics, tumor pathology, treatment strategies used, and survival outcomes were analyzed. Kaplan-Meier curves were estimated using newsurv macros in SAS.</p><p><strong>Results: </strong>The study included a total of 65 patients with PACC. The median age at diagnosis was 66 years. Almost half of the patients (48%) presented with resectable/borderline-resectable disease (n = 28). Five-year overall survival (OS) for resectable/borderline-resectable, locally advanced/unresectable, and metastatic disease were 72.0%, 21.6%, and 20.9%, respectively. Somatic and germline next-generation sequencing identified numerous potentially actionable targets including homologous recombination (43% somatic, 33% germline), <i>RAF</i> alterations (29% somatic), and mismatch repair (14% somatic).</p><p><strong>Conclusion: </strong>Our findings underscore the heterogeneity and aggressive nature of PACC. Despite the improved prognosis for patients with resectable/borderline-resectable disease, OS remains poor, particularly for those with locally advanced or metastatic disease. The identification of actionable molecular targets in a significant proportion of patients highlights the potential for personalized therapeutic approaches. Future research should focus on tailored treatment strategies to exploit these molecular vulnerabilities, which may offer new options for improving outcomes in this rare malignancy.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400450"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949297","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":"Coding Variants of the Genitourinary Development Gene <i>WNT9B</i> Carry High Risk for Prostate Cancer.","authors":"William D Dupont, Angela L Jones, Jeffrey R Smith","doi":"10.1200/PO-24-00569","DOIUrl":"https://doi.org/10.1200/PO-24-00569","url":null,"abstract":"<p><strong>Purpose: </strong>Considerable genetic heterogeneity is currently thought to underlie hereditary prostate cancer (HPC). Most families meeting criteria for HPC cannot be attributed to currently known pathogenic variants.</p><p><strong>Methods: </strong>To discover pathogenic variants predisposing to prostate cancer, we conducted a familial case-control association study using both genome-wide single-allele and identity-by-descent analytic approaches. Sequence of high-risk haplotype carriers was used for variant detection. Candidate pathogenic variants were tested for association with prostate cancer across independent biobanks for replication of observations.</p><p><strong>Results: </strong>Pathogenic variants within <i>WNT9B</i> were associated with familial prostate cancer and observations replicated within four of four independent biobanks. <i>WNT9B</i> E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing a half million patients. <i>WNT9B</i> Q47R was also associated with prostate cancer with genome-wide significance among Finns, for which identity-by-descent analyses confirmed a founder effect. <i>WNT9B</i> shares an unexpected commonality with the previously established prostate cancer risk genes <i>HOXB13</i> and <i>HNF1B</i>: they are each required for embryonic prostate development. With this recognition, we further evaluated two additional genes known to cause Mendelian genitourinary developmental defects, <i>KMT2D</i> and <i>DHCR7</i>. These too were nominally associated with prostate cancer under meta-analyses.</p><p><strong>Conclusion: </strong><i>WNT9B</i> and additional genes that are required for early genitourinary development are also involved in the later development of prostate cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400569"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059086","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":"Optimizing Radiotherapy Timing for Nasopharyngeal Carcinoma: The Impact of Radiation Scheduling on Survival.","authors":"Ying Li, Youliang Weng, Zongwei Huang, Lishui Wu, Siqi Xu, Yingjie Xie, Haolan Li, Jinghua Lai, Dan Hu, Sufang Qiu","doi":"10.1200/PO-24-00603","DOIUrl":"10.1200/PO-24-00603","url":null,"abstract":"<p><strong>Purpose: </strong>Chronoradiobiology has emerged as a potential field of study with therapeutic implications for cancer treatment. We aimed to investigate the association between radiation chronotherapy and the efficacy and toxicity of patients with nasopharyngeal carcinoma (NPC).</p><p><strong>Patients and methods: </strong>Patients with nonmetastatic NPC treated with intensity-modulated radiotherapy in Fujian Cancer Hospital between January 2017 and December 2019 were included. Propensity score matching (PSM) with 1:1:1 was used to account for selection bias. Cox regression analysis was performed to explore the impact of radiotherapy timing on patient survival. Sensitivity analysis was implemented to determine the size and directional stability.</p><p><strong>Results: </strong>One thousand forty patients met study inclusion criteria and 332 patients were included in a PSM cohort. In the unmatched cohort analysis, morning radiotherapy exhibited a significantly superior overall survival (OS) outcome (hazard ratio [HR], 0.60 [95% CI, 0.40 to 0.91], adjusted log-rank <i>P</i> = .028) than the afternoon one. After PSM analysis, it was observed that individuals undergoing radiotherapy in the afternoon group (HR, 5.88 [95% CI, 2.55 to 13.58], adjusted log-rank <i>P</i> = .004) and the night group (HR, 4.81 [95% CI, 1.91 to 12.11], adjusted log-rank <i>P</i> = .018) displayed a tendency toward shorter OS compared with the morning group. No significant differences in acute treatment-related adverse effects were observed among the three groups. Morning radiotherapy demonstrated consistent robustness in the multivariable analysis, thereby establishing an association with higher OS. The directionality of the effect size was consistent across sensitivity analysis.</p><p><strong>Conclusion: </strong>These results underscore the potential benefits of scheduling radiotherapy in the morning for NPC management, although prospective studies are needed to confirm these findings.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400603"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948851","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":"Reply to: Addressing Bias in Feature Importance: A Hybrid Approach for Risk Prediction in Prognostic Survival Models.","authors":"Ge Zhang, Shiqian Zhang, Haonan Zhang, Ruhao Wu, Haoze Zheng","doi":"10.1200/PO-24-00875","DOIUrl":"https://doi.org/10.1200/PO-24-00875","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400875"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948919","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":"Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.","authors":"Stephen J Luen, Lauren C Brown, Courtney T van Geelen, Peter Savas, Roswitha Kammler, Patrizia Dell'Orto, Olivia Biasi, Alan S Coates, Richard D Gelber, Beat Thürlimann, Marco Colleoni, Gini F Fleming, Prudence A Francis, Meredith M Regan, Giuseppe Viale, Sherene Loi","doi":"10.1200/PO-24-00599","DOIUrl":"10.1200/PO-24-00599","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.</p><p><strong>Methods: </strong>This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.</p><p><strong>Results: </strong>A total of 1,795 tumors were evaluable for this study (BIG 1-98 n = 520, SOFT n = 1,275). The frequency of HER2-low tumors was 37% and 21% in the postmenopausal BIG 1-98 and premenopausal SOFT cohorts, respectively. There were no significant differences in clinicopathologic variables between HER2-low and HER2-zero groups which was consistent across both trials. There was no significant difference in risk of distant recurrence for patients with HER2-low tumors versus HER2-zero tumors (5-year % distant recurrence-free 94.0% <i>v</i> 92.8%, <i>P</i> = .61, in BIG 1-98; 89.4% <i>v</i> 92.7%, <i>P</i> = .31, in SOFT, respectively). Somatic genomic profiles were similar with the exception of <i>MAP3K1</i> mutations which were more frequent in HER2-zero tumors (BIG 1-98 19% <i>v</i> 5%, SOFT 11% <i>v</i> 6%). Both <i>ERBB2</i> copy number and <i>ERBB2</i> gene expression abundance were significantly higher in HER2-low tumors compared with HER2-zero tumors; however, the absolute difference was small. Correlation between <i>ERBB2</i> copy number values and gene expression was modest (<i>r</i> = 0.17).</p><p><strong>Conclusion: </strong>In two large clinical trials with centrally reviewed HER2 IHC, our findings do not support HER2-low breast cancer as a distinct clinical or biologic entity among HR+HER2- early breast cancers. Absolute differences in median <i>ERBB2</i> copy number levels or gene expression are small and of unclear biologic relevance.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400599"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033114","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}