低er转移性乳腺癌的预后和生物学特征：来自多中心队列和TONIC试验的结果

IF 10.2 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2025-09-04 DOI:10.1158/1078-0432.ccr-25-1796

Federica Miglietta,Manon De Graaf,Claudio Vernieri,Federico Piacentini,Matilde Cacciatore,Andrea Botticelli,Andrea Vingiani,Giuseppe Fotia,Lorenzo Nicolè,Gaia Griguolo,Tommaso Giarratano,Davide Massa,Valerio Pellegrini,Francesca Schiavi,Francesca Porra,Matteo Fassan,Giancarlo Pruneri,Angelo Paolo Dei Tos,Valentina Guarneri,Marleen Kok,Maria Vittoria Dieci

{"title":"低er转移性乳腺癌的预后和生物学特征：来自多中心队列和TONIC试验的结果","authors":"Federica Miglietta,Manon De Graaf,Claudio Vernieri,Federico Piacentini,Matilde Cacciatore,Andrea Botticelli,Andrea Vingiani,Giuseppe Fotia,Lorenzo Nicolè,Gaia Griguolo,Tommaso Giarratano,Davide Massa,Valerio Pellegrini,Francesca Schiavi,Francesca Porra,Matteo Fassan,Giancarlo Pruneri,Angelo Paolo Dei Tos,Valentina Guarneri,Marleen Kok,Maria Vittoria Dieci","doi":"10.1158/1078-0432.ccr-25-1796","DOIUrl":null,"url":null,"abstract":"PURPOSE\r\nTo assess prognosis of ER-low expression and its dynamics in HER2- metastatic breast cancer (BC) and to compare sensitivity to nivolumab between ER-low and triple-negative (TN) BC.\r\n\r\nEXPERIMENTAL DESIGN\r\nTwo cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic BC, and one prospective cohort of 110 patients with ER<10%/HER2- metastatic BC enrolled in the TONIC trial (testing nivolumab). Endpoints were: overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort; progression-free survival (PFS), OS, and clinical benefit rate (CBR) in the TONIC trial.\r\n\r\nRESULTS\r\nER-low BC were 7.3% of retrospective cases, 15/110 of the TONIC. In the retrospective cohort, patients with ER-low BC had significantly poorer OS (p<0.001) and numerically shorter PRS (p=0.230) compared to ER+/HER2- BC, and numerically longer OS (p=0.098) and significantly longer PRS (p=0.017) compared to TNBC. In the TONIC, patients with ER-low BC, compared to TN, showed similar response to nivolumab (CBR: 20.0% vs 22.1%, p=1), PFS (median 1.7 vs 2.0 months, p=0.5) and OS (median 5.3 vs 8.6 months, p=0.3). Among patients with primary ER+/HER2- BC (n=565), the conversion towards ER-low or TNBC at metastasis conferred independent negative prognostic impact both for OS (p=0.002 and 0.001, respectively) and PRS (p=0.018 and p=0.001, respectively).\r\n\r\nDISCUSSION\r\nWe provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic BC. We offered insights into sensitivity to antiPD1 in metastatic BC, showing that patients with ER-low BC have comparable likelihood of responding to nivolumab as those with TNBC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"19 1","pages":""},"PeriodicalIF":10.2000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prognosis and biological characteristics of ER-low metastatic breast cancer: results from a multicenter cohort and the TONIC trial.\",\"authors\":\"Federica Miglietta,Manon De Graaf,Claudio Vernieri,Federico Piacentini,Matilde Cacciatore,Andrea Botticelli,Andrea Vingiani,Giuseppe Fotia,Lorenzo Nicolè,Gaia Griguolo,Tommaso Giarratano,Davide Massa,Valerio Pellegrini,Francesca Schiavi,Francesca Porra,Matteo Fassan,Giancarlo Pruneri,Angelo Paolo Dei Tos,Valentina Guarneri,Marleen Kok,Maria Vittoria Dieci\",\"doi\":\"10.1158/1078-0432.ccr-25-1796\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"PURPOSE\\r\\nTo assess prognosis of ER-low expression and its dynamics in HER2- metastatic breast cancer (BC) and to compare sensitivity to nivolumab between ER-low and triple-negative (TN) BC.\\r\\n\\r\\nEXPERIMENTAL DESIGN\\r\\nTwo cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic BC, and one prospective cohort of 110 patients with ER<10%/HER2- metastatic BC enrolled in the TONIC trial (testing nivolumab). Endpoints were: overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort; progression-free survival (PFS), OS, and clinical benefit rate (CBR) in the TONIC trial.\\r\\n\\r\\nRESULTS\\r\\nER-low BC were 7.3% of retrospective cases, 15/110 of the TONIC. In the retrospective cohort, patients with ER-low BC had significantly poorer OS (p<0.001) and numerically shorter PRS (p=0.230) compared to ER+/HER2- BC, and numerically longer OS (p=0.098) and significantly longer PRS (p=0.017) compared to TNBC. In the TONIC, patients with ER-low BC, compared to TN, showed similar response to nivolumab (CBR: 20.0% vs 22.1%, p=1), PFS (median 1.7 vs 2.0 months, p=0.5) and OS (median 5.3 vs 8.6 months, p=0.3). Among patients with primary ER+/HER2- BC (n=565), the conversion towards ER-low or TNBC at metastasis conferred independent negative prognostic impact both for OS (p=0.002 and 0.001, respectively) and PRS (p=0.018 and p=0.001, respectively).\\r\\n\\r\\nDISCUSSION\\r\\nWe provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic BC. We offered insights into sensitivity to antiPD1 in metastatic BC, showing that patients with ER-low BC have comparable likelihood of responding to nivolumab as those with TNBC.\",\"PeriodicalId\":10279,\"journal\":{\"name\":\"Clinical Cancer Research\",\"volume\":\"19 1\",\"pages\":\"\"},\"PeriodicalIF\":10.2000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1078-0432.ccr-25-1796\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-25-1796","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

目的探讨er低表达在HER2转移性乳腺癌（BC）中的预后及其动态，并比较er低表达和三阴性（TN） BC对纳武单抗的敏感性。实验设计分析了两个队列：一个是982例HER2转移性BC患者的多中心队列，另一个是110例ER<10%/HER2转移性BC患者的前瞻性队列，纳入了TONIC试验（测试纳武单抗）。终点为：回顾性队列中的总生存期（OS）和复发后生存期（PRS）；TONIC试验的无进展生存期（PFS）、OS和临床获益率（CBR）。结果低BC占回顾性病例的7.3%，占TONIC病例的15/110。在回顾性队列中，与ER+/HER2- BC相比，ER-低BC患者的OS较差（p<0.001）， PRS较短（p=0.230），而与TNBC相比，ER-低BC患者的OS较长（p=0.098）， PRS较长（p=0.017）。在TONIC中，与TN相比，er -低BC患者对纳武单抗（CBR: 20.0% vs 22.1%, p=1）、PFS（中位1.7 vs 2.0个月，p=0.5）和OS（中位5.3 vs 8.6个月，p=0.3）的反应相似。在原发性ER+/HER2- BC患者（n=565）中，转移时向ER-低或TNBC的转化对OS（分别为p=0.002和0.001）和PRS（分别为p=0.018和p=0.001）的预后均有独立的负面影响。讨论：我们提供了er低表达在HER2转移性BC患者中的预后作用及其动态的证据。我们提供了对转移性BC抗pd1敏感性的见解，表明er -低BC患者与TNBC患者对纳武单抗的反应可能性相当。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Prognosis and biological characteristics of ER-low metastatic breast cancer: results from a multicenter cohort and the TONIC trial.

PURPOSE To assess prognosis of ER-low expression and its dynamics in HER2- metastatic breast cancer (BC) and to compare sensitivity to nivolumab between ER-low and triple-negative (TN) BC. EXPERIMENTAL DESIGN Two cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic BC, and one prospective cohort of 110 patients with ER<10%/HER2- metastatic BC enrolled in the TONIC trial (testing nivolumab). Endpoints were: overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort; progression-free survival (PFS), OS, and clinical benefit rate (CBR) in the TONIC trial. RESULTS ER-low BC were 7.3% of retrospective cases, 15/110 of the TONIC. In the retrospective cohort, patients with ER-low BC had significantly poorer OS (p<0.001) and numerically shorter PRS (p=0.230) compared to ER+/HER2- BC, and numerically longer OS (p=0.098) and significantly longer PRS (p=0.017) compared to TNBC. In the TONIC, patients with ER-low BC, compared to TN, showed similar response to nivolumab (CBR: 20.0% vs 22.1%, p=1), PFS (median 1.7 vs 2.0 months, p=0.5) and OS (median 5.3 vs 8.6 months, p=0.3). Among patients with primary ER+/HER2- BC (n=565), the conversion towards ER-low or TNBC at metastasis conferred independent negative prognostic impact both for OS (p=0.002 and 0.001, respectively) and PRS (p=0.018 and p=0.001, respectively). DISCUSSION We provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic BC. We offered insights into sensitivity to antiPD1 in metastatic BC, showing that patients with ER-low BC have comparable likelihood of responding to nivolumab as those with TNBC.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.