| 基本情報/Basic information |
| 一般向け試験名/Public title |
CDK4/6阻害剤治療前後の腫瘍組織及び、FGF・FGFR mutation/amplificationを認めたLuminal又はTNBC症例を対象としたホルモン療法耐性、化学療法効果の予測性の探索的研究（JBCRG-C07-A1） |
An Exploratory Study a) using gene expression analysis to assess the Predictability of Resistance to Hormone Therapy and Chemotherapy sensitivity in Luminal Breast Cancer Patients who have a treatment history of CDK4/6 Inhibition and b) investigating patients with luminal or triple negative breast cancer showing FGF - FGFR Mutation/Amplification detected using FoundationOne Comprehensive Gene Expression Analysis |
| 一般向け試験名略称/Acronym |
JBCRG-C07-A1（REIWA2 study） |
JBCRG-C07-A1(REIWA2 study) |
| 科学的試験名/Scientific Title |
CDK4/6阻害剤治療前後の腫瘍組織及び、FGF・FGFR mutation/amplificationを認めたLuminal又はTNBC症例を対象としたホルモン療法耐性、化学療法効果の予測性の探索的研究（JBCRG-C07-A1） |
An Exploratory Study a) using gene expression analysis to assess the Predictability of Resistance to Hormone Therapy and Chemotherapy sensitivity in Luminal Breast Cancer Patients who have a treatment history of CDK4/6 Inhibition and b) investigating patients with luminal or triple negative breast cancer showing FGF - FGFR Mutation/Amplification detected using FoundationOne Comprehensive Gene Expression Analysis |
| 科学的試験名略称/Scientific Title:Acronym |
JBCRG-C07-A1（REIWA2 study） |
JBCRG-C07-A1(REIWA2 study) |
| 試験実施地域/Region |
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| 目的/Objectives |
| 目的1/Narrative objectives1 |
本研究は、Luminal乳がんを対象として、CDK4/6阻害剤使用後の生物学的悪性度の変化を、FoundationOne/EMT score/IO subtypeを用いることで評価可能であるかを検討する。さらに、それらをretrospectiveに臨床経過と相関させることにより、ホルモン療法の耐性予測、化学療法の効果予測になりうるかを検討する。また、CDK4/6阻害剤使用後に活性化し、予後不良因子とされるFGF/FGFRシグナル経路に注目し、その生物学的理解を深め、Luminal乳がんの悪性度との相関を評価する。TNBCにおいては、molecular subtypeとFGFR mutation/amplificationとmolecular Subtype との相関を見ることで、より臨床的に意義のある分類が可能か検討を行う。 |
To determine whether the FoundationOne results, EMT score and the IO subtype can be used to evaluate the changes in the biological malignancy of tumors after treatment with CDK4/6 inhibitors, which are commonly used as a first and second-line treatment for recurrent luminal breast cancer. The study will also focus on the FGF/FGFR signaling pathway, which is activated after the use of CDK4/6 inhibitors and is considered a poor prognostic factor, in order to improve the biological understanding of this pathway and evaluate its correlation with the malignancy of luminal breast cancer. In addition, this study will examine whether diverse TNBC cases can be classified more clearly by evaluating the correlation of cases with molecular subtype and mutation. |
| 目的2/Basic objectives2 |
その他/Others |
| 目的2 -その他詳細/Basic objectives -Others |
・CDK 4/6阻害剤使用前後でEMT Score/IOsignatureを測定することにより、その経時的変化を含め、ホルモン療法耐性、化学療法効果の予測性について臨床情報との関連。
・CDK4/6阻害剤治療前後でのFGF/FGFR遺伝子及び関連遺伝子の発現量、FGF/FGFR経路の活性化の変化。
・CDK4/6阻害剤使用後の再発乳がんにおける、FGF/FGFR遺伝子及び関連遺伝子の発現、FGF/FGFR経路の活性化と薬物治療への抵抗性，耐性獲得及び予後との相関。
・FoundationOneによる遺伝子変異解析及びRNAseq等による網羅的遺伝子発現解析による、原発巣と再発巣での経時的な腫瘍変化。
・TNBC症例における、FGFR mutation/amplificationとmolecular subtypeとの相関。
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･To examine the changes in the expression levels of the FGF/FGFR genes and related genes before and after treatment with CDK4/6 inhibitors.
･To measure the EMT score and IO signature, and evaluate its ability to predict resistance to hormone therapy and the effect of chemotherapy through comparatively analysis.
･To examine the correlation between luminal breast cancer cases with confirmed FGFR mutation/amplification and cases that showed activation after CDK4/6 inhibitor treatment.
･To examine the correlation with molecular subtypes in TNBC cases with confirmed FGFR mutation/amplification.
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| 試験の性質1/Trial characteristics_1 |
探索的/Exploratory |
| 試験の性質2/Trial characteristics_2 |
その他/Others |
| 試験のフェーズ/Developmental phase |
該当せず/Not applicable |
| 評価/Assessment |
| 主要アウトカム評価項目/Primary outcomes |
・CDK 4/6阻害剤使用前後でEMT Score/IOsignatureを測定することにより、その経時的変化を含め、ホルモン療法耐性、化学療法効果の予測性について臨床情報との関連。
・CDK4/6阻害剤治療前後でのFGF/FGFR遺伝子及び関連遺伝子の発現量、FGF/FGFR経路の活性化の変化。
・CDK4/6阻害剤使用後の再発乳がんにおける、FGF/FGFR遺伝子及び関連遺伝子の発現、FGF/FGFR経路の活性化と薬物治療への抵抗性，耐性獲得及び予後との相関。
・FoundationOneによる遺伝子変異解析及びRNAseq等による網羅的遺伝子発現解析による、原発巣と再発巣での経時的な腫瘍変化。
・TNBC症例における、FGFR mutation/amplificationとmolecular subtypeとの相関。
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･To examine the changes in the expression levels of the FGF/FGFR genes and related genes before and after treatment with CDK4/6 inhibitors.
･To examine the correlation between the expression of FGF/FGFR genes and related genes and the acquisition of resistance to drug treatments and prognosis in recurrent breast cancer after treatment with CDK4/6 inhibitors.
･To measure the EMT score and IO signature, and evaluate its ability to predict resistance to hormone therapy and the effect of chemotherapy through comparatively analysis with the clinical data.
･To evaluate the changes over time in the tumors through gene mutation analysis by FoundationOne and comprehensive gene expression analysis by RNA-seq in primary and recurrent lesions.
･To examine the correlation between luminal breast cancer cases with confirmed FGFR mutation/amplification and cases that showed activation after CDK4/6 inhibitor treatment.
･To examine the correlation with molecular subtypes in TNBC cases with confirmed FGFR mutation/amplification.
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| 副次アウトカム評価項目/Key secondary outcomes |
・EMT scoreによる全生存期間の予測能
・IO subtypeによる全生存期間の予測能
・RNA-seqデータを用い、網羅的遺伝子発現解析を原発巣と再発巣で比較し、ホルモン耐性に対する新たなbiomarkerの構築を試みる。具体的にはTwo-sample t-tests施行し、FDR0.01-0.05の区間で明らかに2群間の差を認める遺伝子群に対し、Ingenuity Pathway Analysis (IPA)を行い、その生物学的特徴を解明し、biomarkerとなりうるか検討を行う。
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･The predictability of overall survival based on the EMT score.
･The predictability of overall survival based on the IO subtype.
･The primary and recurrence lesions will be compared by comprehensive gene expression analysis using RNA-seq data in an attempt to construct a novel biomarker for hormone resistance. Specifically, two-sample t-tests will be performed on the genes, and Ingenuity Pathway Analysis (IPA) will be performed for gene groups that show clear differences between the two types of lesions in the FDR0.01-0.05 range in order to elucidate their biological characteristics and determine whether they can be used as biomarkers.
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| 介入/Intervention |
| 群数/No. of arms |
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| 介入の目的/Purpose of intervention |
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| 介入の種類/Type of intervention |
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| 介入1/Interventions/Control_1 |
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| 介入2/Interventions/Control_2 |
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| 介入3/Interventions/Control_3 |
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| 介入4/Interventions/Control_4 |
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| 介入5/Interventions/Control_5 |
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| 介入6/Interventions/Control_6 |
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| 介入7/Interventions/Control_7 |
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| 介入8/Interventions/Control_8 |
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| 介入9/Interventions/Control_9 |
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| 介入10/Interventions/Control_10 |
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| 適格性/Eligibility |
| 年齢（下限）/Age-lower limit |
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| 年齢（上限）/Age-upper limit |
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| 性別/Gender |
男女両方/Male and Female |
| 選択基準/Key inclusion criteria |
1.JBCRG-C07（REIWA）試験に参加したLuminalコホートで、CDK4/6阻害剤使用歴があり、原発巣の組織サンプルかCDK4/6阻害剤使用後の再発巣の組織サンプルのいずれかでFoundationOne検査が施行されており、原発巣、再発巣いずれの組織サンプルも提出可能な症例。
2.JBCRG-C07（REIWA）試験に参加したTNBコホートでFGFR mutation/amplificationを認めた症例。組織サンプルも提出可能な症例。
3.JBCRG-C07（REIWA）試験参加の有無に問わず、CDK4/6阻害剤使用前後の原発巣―再発巣のペアサンプルの提出が可能なもの。
4.文書による同意が得られた症例。
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(1)A patient in the Luminal cohort of the JBCRG07 observational study who has received treatment with CDK4/6 inhibitors and has undergone FoundationOne testing using a sample of the recurrent lesion after treatment and a patient in the Luminal cohort of the JBCRGC07 observational study who has undergone FoundationOne testing using a sample of the primary lesion, and has a sample of the recurrent lesion tissue taken after CDK4/6 inhibitor use in clinical practice that can be submitted.
(2)A patient in the TNBC cohort of the JBCRGC07 observational study with confirmed FGFR mutation/amplification.
(3)With or without participation in the JBCRG-C07 (REIWA) exam, a patient who can submit a pair sample of primary lesion and recurrent lesion before and after the use of CDK4 / 6 inhibitor.
(4)Cases for which written consent was obtained.
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| 除外基準/Key exclusion criteria |
担当医が本研究の登録に不適当と考える症例。 |
Cases deemed unsuitable for enrollment in this study by the Principal Investigators in each institution. |
| 目標参加者数/Target sample size |
50 |
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