PO.CL12.02 · 临床研究

雌激素受体阳性、HER2低表达乳腺癌的基因组、免疫和临床特征：NextGIM试验最新进展

Genomic, immune, and clinical characterization of estrogen receptor-positive, HER2-low breast cancer: The NextGIM trial latest updates

编号 7907 展板 12 时间 4/22 09:00–12:00 区域 Section 48 主讲 Barbara Cardinali, PhD

分会场 Translational Biomarkers and Emerging Molecular Approaches

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作者与单位 Authors & Affiliations

Barbara Cardinali¹, Alice Stella¹, Chiara Molinelli¹, Marco Bruzzone¹, Yanina Lizet Castillo¹, Francesca Pitto¹, Barbara Massa¹, Simona Pigozzi², Andrea Sciutto¹, Giorgia Anselmi¹, Maria Dono¹, Virna Maltoni², Benedetta Conte³, Giulia Buzzatti¹, Davide Soldato¹, Gaia Griguolo⁴, Valentina Guarneri⁴, Mario Giuliano⁵, Caterina Marchiò⁶, Fabio Puglisi⁷, Lorenzo Gerratana⁷, Francesca Poggio¹, Lucia Del Mastro¹

¹IRCCS Ospedale Policlinico San Martino, Genova, Italy,²University of Genova, Genova, Italy,³University of Piemonte Orientale, Novara, Italy,⁴Institute of Oncology IOV-IRCCS, Padova, Italy,⁵University of Naples "Federico II", Naples, Italy,⁶FPO Istituto Candiolo (IRCCS), Candiolo, Italy,⁷Centro di Riferimento Oncologico IRCCS, Aviano, Italy

摘要 Abstract

中文摘要

背景：约47-65%的雌激素受体阳性（ER+）/HER2阴性乳腺癌（BC），尽管因缺乏HER2基因扩增而被归类为HER2阴性，但表现出低水平的HER2表达（称为HER2低表达BC），免疫组化（IHC）为1+或2+而无扩增评分。最近，又提出了一个额外的亚类—HER2超低表达—用于HER2 IHC-0且<10%肿瘤细胞染色的肿瘤。新出现的证据表明，HER2低表达和HER2超低表达BC与HER2无表达BC相比可能代表生物学上不同的实体。在此，我们展示NextGIM试验的最新进展，这是一项回顾性、多中心转化研究，旨在全面刻画ER+/HER2低表达BC的特征。方法：来自入组GIM（意大利乳腺癌协作组，Gruppo Italiano Mammella）研究者组三项随机临床试验（GIM2、GIM4和GIM10）的患者原发肿瘤样本，按照ASCO/CAP及TILs工作组指南重新评估HER2表达和肿瘤浸润淋巴细胞（TILs）。同时，使用NanoString平台上的nCounter Breast Cancer 360 Panel进行基因表达谱分析。临床和生存数据将被更新和整合，以评估潜在的预后标志物并研究治疗耐药机制。结果：迄今为止，在参与中心筛选的共283例患者中，208份样本经病理和RNA质量/数量评估后被认为适合进行分子分析。已在179份样本中重新评估HER2表达。诊断时，HER2分类为：45.8% HER2阴性（IHC未指定）、26.8% HER2-0、19.6% HER2-1+、7.8% HER2-2+。经病理重新评估后，分布转变为58.7% HER2无表达、20.7% HER2超低表达、15.1% HER2 1+、5.0% HER2 2+、0.6% HER2 3+。值得注意的是，HER2无表达BC在较陈旧的存档样本（2011年之前）中更为普遍。与HER2-1+和HER2-2+相比，TILs水平≤1%在HER2无表达和HER2超低表达肿瘤中更常见（59.1%和67.6% vs. 25.9%和55.6%）。已完成208例的基因组分析，数据分析正在进行中。将在数据集完成后对分子、病理和临床数据进行整合分析。结论：迄今为止从HER2重新评估获得的结果表明，样本采集与重新评估之间的时间间隔可影响组织抗原性和免疫组化结果，在为治疗目的重新评估HER2状态时应予以考虑。总体而言，本研究预期通过整合基因组、免疫学和临床信息，验证HER2低表达和超低表达作为预后/预测生物标志物，以支持个体化治疗。

查看英文原文 English abstract

Background: Approximately 47-65% of estrogen receptor-positive (ER+)/HER2-negative breast cancers (BC), although classified as HER2-negative due to the absence of HER2 gene amplification, exhibit low levels of HER2 expression (referred to as HER2-low BC) with immunohistochemistry (IHC) 1+ or 2+ without amplification scores. More recently, an additional subclass-HER2-ultralow-has been proposed for tumors with HER2 IHC-0 and <10% tumor cell staining. Emerging evidence indicates that HER2-low and HER2-ultralow BC may represent biologically distinct entities compared with HER2-null BC. Here, the latest updates of the NextGIM trail, a retrospective, multicenter translational study designed to comprehensively characterize ER+/HER2-low BC, are presented. Methods: Primary tumor samples from patients enrolled in three randomized clinical trials (GIM2, GIM4, and GIM10) of the GIM (Gruppo Italiano Mammella) Investigator Group, underwent re-assessment of HER2 expression and tumor-infiltrating lymphocytes (TILs) in accordance with ASCO/CAP and TILs Working Group guidelines. In parallel, gene expression profiling was performed using the nCounter Breast Cancer 360 Panel on the NanoString platform. Clinical and survival data will be updated and integrated to evaluate potential prognostic markers and to investigate mechanisms of treatment resistance. Results: To date, from a total of 283 patients selected at participating centres, 208 samples were deemed suitable for molecular analyses after pathological and RNA quality/quantity assessment. HER2 expression has been re-evaluated in 179 samples. At diagnosis, HER2 classification was: 45.8% HER2-negative (IHC not specified), 26.8% HER2-0, 19.6% HER2-1+, and 7.8% HER2-2+. After pathological reassessment, the distribution shifted to 58.7% HER2-null, 20.7% HER2-ultralow, 15.1% HER2 1+, 5.0% HER2 2+, and 0.6% HER2 3+. Notably, HER2-null BC resulted more prevalent in older archival samples (before 2011). TILs levels ≤1% were more frequently observed in HER2-null and HER2-ultralow tumors compared with HER2-1+ and HER2-2+ (59.1% & 67.6% vs. 25.9% & 55.6%).. Genomic profiling has been completed for 208 cases and data analyses are ongoing. An integrated analysis of molecular, pathological and clinical data will be conducted upon completion of the dataset. Conclusion: The results obtained so far from HER2 re-evaluation has indicated that the interval between sample collection and reassessment can affect tissue antigenicity and immunohistochemistry results, and should be considered when re-evaluating HER2 status for therapeutic purposes. Overall, the study is expected, integrating genomic, immunological, and clinical information, to validate HER2-low and -ultralow expression as prognostic/predictive biomarkers to support personalized treatment.

利益披露 Disclosure

B. Cardinali, Menarini Silicon Biosystem ), Travel. A. Stella, None. C. Molinelli, Daiichi Sankyo Other, Consulting Fee . Seagen Other, Medical Writing fees . Astrazeneca Travel, support for attending medical conferences. Menarini Travel, support for attending medical conferences. Accademia Nazionale di Medicina Other, Speaker honoraria . M. Bruzzone, None. Y. Castillo, Daichii Sanchyo Other, Advisory Board. F. Pitto, Daichii Sanchyo Other, Advisory Board. B. Massa, Genomic Health Other, Advisory Board. S. Pigozzi, None.. A. Sciutto, None.. G. Anselmi, None.. M. Dono, None.. V. Maltoni, None. B. Conte, Pfizer Travel. Roche Travel. Novartis Travel. Gilead ). AstraZeneca Other, Speaker Fee. Menarini Other, Speaker Fee. Varacyte Other, Speaker Fee. G. Buzzatti, Novartis Travel. Menarini Travel. AstraZeneca Other, Speaker Honoraria. Gentili Other, Speaker Honoraria. Daiichi Sanchyo Other, Speaker Honoraria. Novartis Other, Speaker Honoraria. D. Soldato, AstraZeneca Other, Honoraria. Novartis Travel. Merck Travel. Daiichi-Sankyo Travel. G. Griguolo, Gilead Travel, Other, advisory role. Seagen Other, advisory role. Menarini Other, advisory role. Eli Lilly Travel, Other, personal fees as an invited speaker. Novartis Travel, personal fees as an invited speaker. MSD Other, personal fees as an invited speaker. AstraZeneca Travel. Daiichi Sankyo Travel. Pfizer Travel. V. Guarneri, AstraZeneca Other, advisory board membership Personal fees as an invited speaker. Daiichi Sankyo Other, advisory board membership Personal fees as an invited speaker. Eli Lilly Other, advisory board membership Personal fees as an invited speaker. Exact Sciences Other, advisory board membership Personal fees as an invited speaker. Menarini Stemline Other, advisory board membership Personal fees as an invited speaker. MSD Other, advisory board membership. Novartis Other, advisory board membership Personal fees as an invited speaker. Pfizer Other, advisory board membership Personal fees as an invited speaker. Roche Other, advisory board membership Personal fees as an invited speaker. Gilead advisory board membership Personal fees as an invited speaker. Abbvie Other, Personal fees as an invited speake. M. Giuliano, AstraZeneca Travel, Other, Consulting/Advisor Honoraria. Daichii Sankyo Other, Consulting/Advisor Honoraria. Eisai Other, Consulting/Advisor . Exact Sciences Other, Consulting/Advisor Honoraria. Gilead Travel, Other, Consulting/Advisor. Gentili Other, Consulting/Advisor. Lilly Travel, Other, Consulting/Advisor Honoraria. Menarini Stemline Other, Consulting/Advisor. MSD Other, Consulting/Advisor Honoraria. Novartis Travel, Consulting/Advisor Honoraria. Pfizer Travel, Other, Consulting/Advisor Honoraria. Roche Other, Consulting/Advisor. Seagen Other, Consulting/Advisor. C. Marchiò, Menarini Other, Advisory Board. Roche Other, Advisory Board. Illumina Other, Advisory Board. F. Puglisi, Amgen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Astrazeneca ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants Honoraria for advisory boards, activities as a speaker, travel grants, research grants Research funding. Bayer ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Daiichi Sankyo ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Celgene ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Eisai ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants Research funding. Eli Lilly ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Exact Sciences ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Gilead ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants. Ipsen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Italfarmaco ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Menarini ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. MSD ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Novartis ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Pierre Fabre ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Pfizer ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Roche ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants; Research Fundings. Seagen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. Takeda ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants. L. Gerratana, AstraZeneca Consulting or Advisory Role. Daiichi Sanckyo Other, Consulting or Advisory Role. Eli Lilly Other, Consulting or Advisory Role. GlaxoSmithKline Other, Consulting or Advisory Role. Incyte Other, Consulting or Advisory Role. Novartis Travel, Other, Consulting or Advisory Role. Pfizer Other, Consulting or Advisory Role. Merck Sharp & Dohme Other, Consulting or Advisory Role. Menarini Stemline Travel, Consulting or Advisory Role. Abbvie Consulting or Advisory Role. Gilead ), Travel, Consulting or Advisory Role. F. Poggio, Pfizer Other, Speaker Fee Advisory board. Eli Lilly Other, Speaker Fee. Novartis Travel, Other, Speaker Fee. Daiichi Sanckyo Other, Speaker Honoraria. Menarini Other, Speaker Fee. Gilead Travel. Roche Travel, Other, Advisory board. AstraZeneca Other, Advisory board. L. Del Mastro, Eli Lilly ), Other, consulting fees Speaker Honoraria Advisory Board. Novartis ), Other, Speaker Honoraria, Advisory Board. Roche ), Travel, Speaker Honoraria, Advisory Board. Daiichi Sankyo ), Travel, Other, consulting fees, Advisory Board. Seagen ), Other, Speaker Honoraria, Advisory Board. AstraZeneca ), Travel, Other, Speaker Honoraria, Advisory Board. Gilead ), Other, consulting fees, Speaker Honoraria, Advisory Board. Pierre Fabre ), Other, Speaker Honoraria, Advisory Board. Pfizer Travel, Other, Speaker Honoraria, Advisory Board. MSD Other, Speaker Honoraria. Eisai Travel, Other, Speaker Honoraria, Advisory Board. Exact Sciences Other, Speaker Honoraria, Advisory Board. Ibsen Other, Speaker Honoraria. GSK Other, Speaker Honoraria, Advisory Board. Agendia_Stemline Other, Speaker Honoraria, Advisory Board.

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