ESMO Open最新文献

{"title":"Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes","authors":"W. Xu ,&nbsp;G. Birch ,&nbsp;A. Meliki ,&nbsp;V. Moritz ,&nbsp;M. Bharadwaj ,&nbsp;N.R. Schindler ,&nbsp;C. Labaki ,&nbsp;R.M. Saliby ,&nbsp;K. Dinh ,&nbsp;J.T. Horst ,&nbsp;M. Sun ,&nbsp;S. Kashima ,&nbsp;M. Hugaboom ,&nbsp;A. Dighe ,&nbsp;M. Machaalani ,&nbsp;G.-S.M. Lee ,&nbsp;M. Hurwitz ,&nbsp;B.A. McGregor ,&nbsp;M.S. Hirsch ,&nbsp;S.A. Shukla ,&nbsp;D.A. Braun","doi":"10.1016/j.esmoop.2024.104105","DOIUrl":"10.1016/j.esmoop.2024.104105","url":null,"abstract":"<div><h3>Background</h3><div>Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.</div></div><div><h3>Materials and methods</h3><div>We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages. For each primary tumor specimen, paired normal kidneys were also analyzed. Differential gene expression analysis was carried out to investigate NK cell phenotypes and to derive a gene expression signature. Gene signatures from NK cell subclusters of interest were used to interrogate bulk transcriptomic datasets and expression with clinical outcomes. Finally, tumor-infiltrating NK cell function (cytokine production and cytotoxicity) was assessed by isolation of live NK cells from ccRCC tissue, co-culture with K562 target cells, and measurement of cytokine production (interferon-γ) and cytotoxicity (CD107a) markers by flow cytometry.</div></div><div><h3>Results</h3><div>Single-cell transcriptomic data were analyzed from 13 patients with ccRCC (tumor/normal kidney), resulting in 21 139 NK cells. Clustering analysis revealed six NK cell subsets. Bright-like NK cells were significantly enriched in advanced ccRCC compared with localized ccRCC and normal kidney, expressed markers of tissue residency (<em>ZNF683</em>/Hobit, <em>ITGA1</em>/CD49a, <em>CD9</em>, <em>ITGAE</em>/CD103), and had decreased expression of cytotoxicity genes (<em>GZMB</em>/Granzyme-B, <em>PRF1</em>/perforin). In independent cohorts (The Cancer Genome Atlas ccRCC cohort, CheckMate 025), a gene expression score representing this dysfunctional NK cell phenotype was enriched in advanced ccRCC and was associated with worse overall survival. Functional interrogation of tumor-infiltrating NK cells from ccRCC confirmed that tumor-resident CD49a+CD9+ NK cells had impaired cytotoxicity compared with CD49a−CD9− NK cells.</div></div><div><h3>Conclusions</h3><div>A dysfunctional, tumor-resident NK cell phenotype was enriched among patients with metastatic disease and associated with worse survival in patients with advanced ccRCC across multiple patient cohorts. Restoration of NK cell function (via cytokine stimulation or NK cell engineering) could provide a novel avenue for therapeutic intervention against ccRCC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104105"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002144","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":"Factors associated with first-to-second-line attrition among patients with metastatic breast cancer in the real world","authors":"E. Blondeaux ,&nbsp;L. Boni ,&nbsp;G. Chilà ,&nbsp;A. Dri ,&nbsp;R. Caputo ,&nbsp;F. Poggio ,&nbsp;A. Fabi ,&nbsp;G. Arpino ,&nbsp;F. Pravisano ,&nbsp;E. Geuna ,&nbsp;V. Delucchi ,&nbsp;T. Ruelle ,&nbsp;I. Giannubilo ,&nbsp;M. De Laurentiis ,&nbsp;F. Puglisi ,&nbsp;C. Bighin ,&nbsp;M. Lambertini ,&nbsp;F. Montemurro ,&nbsp;L. Del Mastro","doi":"10.1016/j.esmoop.2024.104125","DOIUrl":"10.1016/j.esmoop.2024.104125","url":null,"abstract":"<div><h3>Background</h3><div>Estimating patient attrition across lines of treatment (i.e. the probability that upon treatment failure the patient will not be able to receive a subsequent treatment) may be a valuable tool for optimizing treatment sequencing. We sought to describe the first-to-second-line attrition rate and factors associated with attrition in a real-world cohort of patients with metastatic breast cancer.</div></div><div><h3>Methods</h3><div>The Gruppo Italiano Mammella (GIM)14/BIO-META (NCT02284581) is an ongoing, ambispective observational multicenter study enrolling patients with metastatic breast cancer receiving first-line therapy. In patients experiencing disease progression, attrition was defined as no further anticancer treatment and death within 6 months from the end of first-line therapy. The attrition rate from the first-to-second line was studied by descriptive analyses and univariate and multivariable logistic models were used to explore potentially predictive factors.</div></div><div><h3>Results</h3><div>From January 2000 to December 2021, 3109 patients with metastatic breast cancer were enrolled in the GIM14/BIO-META study. Among them, 2498 patients experienced first-line treatment failure. Overall, first-to-second line attrition was 9.0% (95% confidence interval 7.9% to 10.1%), with similar attrition for patients with hormone receptor-positive/HER2-negative (8.5%) and HER2-positive (7.1%) breast cancer. Patients with triple-negative disease experienced the highest attrition (13.0%). Age, menopausal status, disease-free interval from primary tumor diagnosis, type of metastatic spread, and tumor subtype independently predicted first-to-second-line attrition.</div></div><div><h3>Conclusions</h3><div>These findings could inform treatment decisions and guide clinical research on treatment sequencing. For instance, patients with the lowest risk of attrition may be the ideal candidates for trials exploring de-escalated first-line regimens, followed by more aggressive treatments upon progression.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104125"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022644","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":"Is pathological response an adequate surrogate marker for survival in neoadjuvant therapy with immune checkpoint inhibitors?","authors":"K. Sugiyama ,&nbsp;A. Gordon ,&nbsp;S. Popat ,&nbsp;A. Okines ,&nbsp;J. Larkin ,&nbsp;I. Chau","doi":"10.1016/j.esmoop.2024.104122","DOIUrl":"10.1016/j.esmoop.2024.104122","url":null,"abstract":"<div><div>Pathological response (PR) is an oncological outcome measure that indicates the therapeutic response to neoadjuvant therapy. In clinical trials involving neoadjuvant or perioperative interventions, overall survival and disease/event-free survival are typically the primary outcome measures. Although some evidence suggests that pathological complete response (pCR) can serve as a surrogate marker for the primary endpoint in prospective trials, it remains uncertain whether pCR is a true surrogate marker for patients with cancer undergoing curative resection across all solid tumours. Here, we review the role of PR as a surrogate marker and its associated methodological issues in the era of perioperative immune checkpoint inhibitors.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104122"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058493","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":"Liver metastases do not predict resistance to the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab in proficient MMR metastatic colorectal cancer: a secondary analysis of the AtezoTRIBE study","authors":"C. Antoniotti ,&nbsp;M. Carullo ,&nbsp;D. Rossini ,&nbsp;F. Pietrantonio ,&nbsp;L. Salvatore ,&nbsp;S. Lonardi ,&nbsp;S. Tamberi ,&nbsp;C. Sciortino ,&nbsp;V. Conca ,&nbsp;M.A. Calegari ,&nbsp;P. Ciracì ,&nbsp;E. Tamburini ,&nbsp;F. Bergamo ,&nbsp;C. Boccaccio ,&nbsp;A. Passardi ,&nbsp;G. Ritorto ,&nbsp;C. Ugolini ,&nbsp;G. Aprile ,&nbsp;J. Galon ,&nbsp;C. Cremolini","doi":"10.1016/j.esmoop.2025.104135","DOIUrl":"10.1016/j.esmoop.2025.104135","url":null,"abstract":"<div><h3>Background</h3><div>Liver metastases (LMs) are related to poor efficacy of immune checkpoint inhibitor (ICI)-containing therapies. In the AtezoTRIBE trial, Immunoscore-Immune-Checkpoint (immunoscore-IC) was a predictor of benefit from atezolizumab in mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC).</div></div><div><h3>Patients and methods</h3><div>In pMMR patients enrolled in the AtezoTRIBE study, we investigated the association of LMs with immune-related biomarkers and treatment outcomes, and the predictive role of immunoscore-IC in the LMs group.</div></div><div><h3>Results</h3><div>Out of 202 pMMR patients, 151 (75%) had LMs. No differences in immune-related features were observed according to the presence or not of LMs, except for a lower prevalence of tumour-infiltrating lymphocytes-high tumours in the LMs group (33% versus 52%, <em>P</em> = 0.03). Worse outcomes were observed among patients with LMs [progression-free survival (PFS), <em>P</em> = 0.002; overall survival (OS), <em>P</em> = 0.011], also in multivariable models. The effect of adding atezolizumab to FOLFOXIRI/bevacizumab was independent from LMs in terms of PFS (<em>P</em>_int = 0.990) and OS (<em>P</em>_int = 0.800). Among patients with pMMR mCRC and LMs, those with immunoscore-IC-high but not those with immunoscore-IC-low tumours achieved benefit from atezolizumab, though in the absence of a statistically significant interaction effect (<em>P</em>_int for PFS and OS = 0.166 and 0.473, respectively).</div></div><div><h3>Conclusions</h3><div>LMs are associated with poor prognosis in pMMR mCRC and do not predict resistance to the addition of atezolizumab to FOLFOXIRI/bevacizumab. Immunoscore-IC seems to retain its predictive impact also among patients with LMs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104135"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133020","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":"An open-label, phase IB/II study of abemaciclib with paclitaxel for tumors with CDK4/6 pathway genomic alterations","authors":"K.H. Kim ,&nbsp;C. Park ,&nbsp;S.-H. Beom ,&nbsp;M.H. Kim ,&nbsp;C.G. Kim ,&nbsp;H.R. Kim ,&nbsp;M. Jung ,&nbsp;S.J. Shin ,&nbsp;S.Y. Rha ,&nbsp;H.S. Kim","doi":"10.1016/j.esmoop.2024.104106","DOIUrl":"10.1016/j.esmoop.2024.104106","url":null,"abstract":"<div><h3>Background</h3><div>Disruption of cyclin D-dependent kinases (CDKs), particularly <em>CDK4/6</em>, drives cancer cell proliferation via abnormal protein phosphorylation. This open-label, single-arm, phase Ib/II trial evaluated the efficacy of the <em>CDK4/6</em> inhibitor, abemaciclib, combined with paclitaxel against <em>CDK4/</em><em>6</em>-activated tumors.</div></div><div><h3>Patients and methods</h3><div>Patients with locally advanced or metastatic solid tumors with <em>CDK4/6</em> pathway aberrations were included. Based on phase Ib, the recommended phase II doses were determined as abemaciclib 100 mg twice daily and paclitaxel 70 mg/m² on days 1, 8, and 15, over 4-week-long cycles. The primary endpoint for phase II was the overall response rate (ORR). The secondary endpoints included the clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Tissue-based next-generation sequencing and exploratory circulating tumor DNA analyses were carried out.</div></div><div><h3>Results</h3><div>Between February 2021 and April 2022, 30 patients received abemaciclib/paclitaxel (median follow-up: 15.7 months), and 27 were included in the efficacy analysis. <em>CDK4/6</em> amplification (50%) and <em>CCND1/3</em> amplification (20%) were common activating mutations. The ORR was 7.4%, with two partial responses, and the CBR was 66.7% (18/27 patients). The median OS and PFS were 9.9 months [95% confidence interval (CI) 5.7-14.0 months] and 3.5 months (95% CI 2.6-4.3 months), respectively. Grade 3 adverse events (50%, 21 events) were mainly hematologic. Genetic analysis revealed a ‘poor genetic status’ subgroup characterized by mutations in key signaling pathways (RAS, Wnt, PI3K, and NOTCH) and/or <em>CCNE</em> amplification, correlating with poorer PFS.</div></div><div><h3>Conclusion</h3><div>Abemaciclib and paclitaxel showed moderate clinical benefits for <em>CDK4/</em><em>6</em>-activated tumors. We identified a poor genetic group characterized by bypass signaling pathway activation and/or <em>CCNE</em> amplification, which negatively affected treatment response and survival. Future studies with homogeneous patient groups are required to validate these findings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104106"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058484","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":"Interobserver consistency and diagnostic challenges in HER2-ultralow breast cancer: a multicenter study","authors":"S. Wu ,&nbsp;J. Shang ,&nbsp;Z. Li ,&nbsp;H. Liu ,&nbsp;X. Xu ,&nbsp;Z. Zhang ,&nbsp;Y. Wang ,&nbsp;M. Zhao ,&nbsp;M. Yue ,&nbsp;J. He ,&nbsp;J. Miao ,&nbsp;Y. Sang ,&nbsp;J. Yan ,&nbsp;W. Pang ,&nbsp;Q. Shao ,&nbsp;Y. Zhang ,&nbsp;M. Zhao ,&nbsp;X. Liu ,&nbsp;P. Wang ,&nbsp;C. Cai ,&nbsp;Y. Liu","doi":"10.1016/j.esmoop.2024.104127","DOIUrl":"10.1016/j.esmoop.2024.104127","url":null,"abstract":"<div><h3>Background</h3><div>Recent advancements in novel antibody–drug conjugates (ADCs) have demonstrated efficacy in patients with human epidermal growth factor receptor 2 (HER2)-ultralow breast cancer (BC), expanding the eligibility for anti-HER2 targeted therapy to include some patients previously categorized as HER2 immunohistochemistry (IHC) 0. This expansion underscores the need for pathologists to accurately differentiate HER2-null and HER2-ultralow.</div></div><div><h3>Materials and methods</h3><div>Thirty-six pathologists from four centers nationwide conducted microscopic visual assessments on HER2 IHC slides from 50 consecutive BC surgical specimens, all previously diagnosed as HER2 IHC 0.</div></div><div><h3>Results</h3><div>The interobserver consistency in differentiating HER2-null from HER2-ultralow, measured by Fleiss κ, was only 0.230—lower than the consistency for combined HER2 IHC 0 cases (Fleiss κ = 0.344) and binary classification (HER2-null versus HER2-non-null; Fleiss κ = 0.292). High agreement for HER2-null versus HER2-ultralow differentiation was achieved in only 4% of cases, while combining them into HER2 IHC 0 raised high agreement cases to 32%, higher than the 18% seen in the binary classification. Consensus among the 36 pathologists aligned with historical scores in 72% of cases; however, when subdividing HER2 IHC 0 into HER2-null and HER2-ultralow, the consistency dropped to 54%.</div></div><div><h3>Conclusions</h3><div>The low consistency among pathologists in distinguishing HER2-null, -ultralow, and 1+ cases may impact patient eligibility for new ADC therapies. To address this challenge, there is a need for improved detection methods, artificial intelligence-assisted quantitative assessments, and larger clinical datasets to refine the definition of HER2-ultralow.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104127"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074154","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":"Sinonasal malignancy: ESMO–EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up☆","authors":"C. Resteghini ,&nbsp;B. Baujat ,&nbsp;P. Bossi ,&nbsp;A. Franchi ,&nbsp;L. de Gabory ,&nbsp;J. Halamkova ,&nbsp;F. Haubner ,&nbsp;J.A.U. Hardillo ,&nbsp;M.A. Hermsen ,&nbsp;N.A. Iacovelli ,&nbsp;R. Maroldi ,&nbsp;S. Mattheis ,&nbsp;A. Moya-Plana ,&nbsp;P. Nicolai ,&nbsp;E. Orlandi ,&nbsp;J. Thariat ,&nbsp;A. Trama ,&nbsp;M.W.M. van den Brekel ,&nbsp;C.M.L. van Herpen ,&nbsp;B. Verillaud ,&nbsp;C. Even","doi":"10.1016/j.esmoop.2024.104121","DOIUrl":"10.1016/j.esmoop.2024.104121","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104121"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453263","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":"ESMO Clinical Practice Guideline interim update on the treatment of locally advanced oesophageal and oesophagogastric junction adenocarcinoma and metastatic squamous-cell carcinoma","authors":"R.L. Obermannová ,&nbsp;T. Leong ,&nbsp;ESMO Guidelines Committee","doi":"10.1016/j.esmoop.2025.104134","DOIUrl":"10.1016/j.esmoop.2025.104134","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104134"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453264","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":"Tumor-infiltrating lymphocytes in HER2-positive breast cancer: potential impact and challenges","authors":"I. Schlam ,&nbsp;S. Loi ,&nbsp;R. Salgado ,&nbsp;S.M. Swain","doi":"10.1016/j.esmoop.2024.104120","DOIUrl":"10.1016/j.esmoop.2024.104120","url":null,"abstract":"<div><h3>Introduction</h3><div>In this review, we evaluate the role of stromal tumor-infiltrating lymphocytes (sTILs) as a biomarker in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, exploring the prognostic and predictive potential in various treatment settings.</div></div><div><h3>Methods</h3><div>Data from multiple clinical trials in the early and metastatic settings, focusing on TILs’ correlation with pathologic complete response (pCR), progression-free survival (PFS), and overall survival across early and metastatic HER2-positive breast cancer were summarized. This review also discusses TILs’ assessment methods, interobserver variability, and emerging technologies to assess TILs.</div></div><div><h3>Results</h3><div>TILs have been identified as a highly reproducible biomarker that predicts pCR in patients receiving neoadjuvant therapy and serves as a prognostic indicator for long-term outcomes in several breast cancer subtypes, including HER2-positive. Studies indicate that higher TIL levels correlate with better recurrence-free survival rates. Despite these findings, there is no consensus on the optimal TIL threshold for clinical decision making, and further research is required on how to incorporate TILs into routine clinical practice.</div></div><div><h3>Conclusions</h3><div>TILs represent a promising biomarker in HER2-positive breast cancer, particularly in early disease settings. This assessment could guide treatment de-escalation or intensification, tailoring therapies to individual patient profiles. Due to their prognostic importance, TILs can be added to pathology reports. However, further validation in clinical trials is essential for the widespread adoption of TILs in clinical practice.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104120"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002212","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":"The prognostic and predictive value of the luminal-like subtype in hormone receptor-positive breast cancer: an analysis of the DATA trial","authors":"S.W.M. Lammers ,&nbsp;S.M.E. Geurts ,&nbsp;K.E.P.E. Hermans ,&nbsp;L.F.S. Kooreman ,&nbsp;A.C.P. Swinkels ,&nbsp;C.H. Smorenburg ,&nbsp;M.J.C. van der Sangen ,&nbsp;J.R. Kroep ,&nbsp;A.H. Honkoop ,&nbsp;F.W.P.J. van den Berkmortel ,&nbsp;W.K. de Roos ,&nbsp;S.C. Linn ,&nbsp;A.L.T. Imholz ,&nbsp;I.J.H. Vriens ,&nbsp;V.C.G. Tjan-Heijnen ,&nbsp;Dutch Breast Cancer Research Group (BOOG) for the DATA investigators","doi":"10.1016/j.esmoop.2025.104154","DOIUrl":"10.1016/j.esmoop.2025.104154","url":null,"abstract":"<div><h3>Background</h3><div>This study determines the prognostic value of the luminal-like subtype in patients with hormone receptor-positive breast cancer and explores whether the efficacy of extended anastrozole therapy differs between patients with luminal A-like versus luminal B-like tumours.</div></div><div><h3>Materials and methods</h3><div>The phase III DATA study (NCT00301457) examined the efficacy of 6 versus 3 years of anastrozole in postmenopausal women with early-stage hormone receptor-positive breast cancer who had received 2-3 years of tamoxifen. Patients with available formalin-fixed paraffin-embedded tissue blocks were identified and classified by immunohistochemical luminal-like subtype. Distant recurrence (DR) and breast cancer-specific mortality (BCSM) were compared by luminal-like subtype and treatment arm using competing risk methods.</div></div><div><h3>Results</h3><div>This study included 788 patients: 491 had a luminal A-like tumour and 297 had a luminal B-like tumour. The median follow-up time was 13.1 years. Patients with luminal B-like tumours experienced a higher risk of DR [subdistribution hazard ratio (sHR) 1.44, 95% confidence interval (CI) 1.03-2.01, <em>P</em> = 0.03] and BCSM (sHR 1.68, 95% CI 1.15-2.45, <em>P</em> = 0.008) than patients with luminal A-like tumours. The efficacy of extended anastrozole therapy differed between patients with luminal A-like tumours (DR: sHR 0.51, 95% CI 0.30-0.88, <em>P</em> = 0.02; BCSM: sHR 0.39, 95% CI 0.19-0.82, <em>P</em> = 0.01) and patients with luminal B-like tumours (DR: sHR 2.09, 95% CI 0.96-4.53, <em>P</em> = 0.06; BCSM: sHR 2.36, 95% CI 0.80-7.00, <em>P</em> = 0.12) (<em>P</em>-interaction = 0.03 and <em>P</em>-interaction = 0.06, respectively).</div></div><div><h3>Conclusion</h3><div>In patients with hormone receptor-positive breast cancer, the luminal B-like subtype was associated with a significantly worse prognosis when compared with the luminal A-like subtype. Extended anastrozole therapy halved the risk of DR and BCSM in patients with luminal A-like tumours, whereas no effect was seen in patients with luminal B-like tumours.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104154"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350063","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}