ON-treatment Single-cell Analysis for the Identification of Early Tumor Response Biomarkers on Prospective Collected Serial Tumor Biopsies in Triple Negative Breast Cancer Patient During Standard Neoadjuvant Chemo-immunotherapy (ONSET)
This study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. The aim is to better understand how cancer cells and immune cells interact and to identify biomarkers that can predict whether a patient will respond to chemo-immunotherapy or develop resistance.
The study assumes that early molecular and spatial changes at the single-cell level can predict treatment response. This knowledge could help doctors adapt therapies, avoiding unnecessary treatment while improving effectiveness. The project seeks to reveal, for the first time, how cellular diversity and spatial relationships contribute to treatment resistance and disease progression.
Tumor samples will be analyzed before treatment, after the first treatment cycle (C1D1), and at surgery. Only the biopsy taken after C1D1 is collected specifically for this study; all other samples come from routine clinical care.
調査の概要
詳細な説明
This exploratory translational study investigates early breast cancer (EBC), focusing on triple-negative (TNBC) and high-risk luminal (ER+/HER2-) subtypes. By integrating single-cell RNA sequencing, using the 10x Genomics platform (or similar technologies if it will be not available at the time of experiment), and spatial imaging analyses from serial tumor biopsies, the project aims to characterize tumor-immune interactions and identify predictive biomarkers of response or resistance to neoadjuvant chemo-immunotherapy.
We hypothesize that early molecular and spatial features, when detected at the single-cell level, can predict treatment sensitivity or resistance. This would enable adaptive therapeutic strategies that minimize overtreatment while maximizing efficacy in EBC. Our goal is to reveal, for the first time, the cellular heterogeneity and spatial interactions that drive therapy resistance and disease progression.
The analysis will be performed on tumor biopsies collected before the start of treatment, after C1D1 and on surgical material. The only tissue sample collected specifically for the study is the biopsy after C1D1.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Giulia Viale, MD
- 電話番号：+390226437627
- メール：callcenter.mammella@hsronline.it
研究場所
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Lombardy
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Milan、Lombardy、イタリア、20132
- IRCCS Ospedale San Raffaele
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コンタクト：
- Giulia Viale, MD
- 電話番号：+390226437627
- メール：callcenter.mammella@hsronline.it
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Female patients aged ≥18 years.
- ECOG performance status 0-1.
Histologically confirmed early breast cancer with one of the following molecular profiles:
- TNBC: ER and PR negative (IHC <10%) and HER2 negative (IHC 0-1+ or FISH non-amplified).
- High-risk luminal (ER+/HER2-): ER positive (IHC ≥10%) HER2 negative (IHC 0-1+ or FISH non-amplified), with high-risk features (e.g., Grade 3, PR-negative, high proliferation, high TILS).
Clinical indication for neoadjuvant treatment according to standard practice:
- TNBC: cT1c and/or cN positive, or cT2 (>2 cm) and/or cN positive (stage II,III).
- High-risk luminal: features as defined above (Grade 3, PR-negative, high proliferation, ER low).
- Ability to understand and sign written informed consent for participation in the study, approved by the local Ethics Committee.
Exclusion Criteria:
- HER2-positive tumors.
- Multifocal tumors - exclusion if a single index lesion cannot be identified and sampled; otherwise allowed if a representative lesion can be biopsied.
- Known metastatic disease. 4 Clinical contraindications to the planned neoadjuvant therapy.
5. Decision for upfront surgery as determined by the multidisciplinary team. 6. Inability to provide informed consent. 7. Pregnancy or breastfeeding. 8. Prior systemic therapy (chemotherapy, immunotherapy, or endocrine therapy) for the current breast cancer before baseline biopsy 9. On-treatment biopsy clinically not feasible or controindicated
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：他の
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
To characterize the dynamic changes in tumor and immune cell populations in TNBC and to prospectively collect serial samples from high-risk luminal (ER+/HER2-) breast cancer patients.
時間枠：Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
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Gene expression levels per single-cell and relative cell clustering (%) by comparing pre-treatment, on-treatment (after first cycle of standard of care neoadiuvant therapy), and post-treatment (surgery or residual disease)
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Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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To correlate single-cell gene expression data with pCR and RD to identify predictive signatures of therapy response
時間枠：Across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
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pCR and RD will be evaluated across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
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Across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- ONSET
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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