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
Breast Cancer Early Stage Breast Cancer (Stage 1-3)
Investigational drug(s) / intervention(s)
on treatment biopsy (after C1)
on treatment biopsy (after C1): Serial tumor tissue collection and analysis for the identification of early tumor response biomarkers. Tumor samples will be obtained at three predefined time points: (i) prior to initiation of treatment (baseline biopsy), (ii) after Cycle 1 Day 1 (C1D1) of therapy, and (iii) at the time of surgery (surgical specimen)
Study summary
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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Female patients aged ≥18 years.
2. ECOG performance status 0-1.
3. 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).
4. 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).
5. Ability to understand and sign written informed consent for participation in the study, approved by the local Ethics Committee.
Exclusion Criteria:
1. HER2-positive tumors.
2. Multifocal tumors - exclusion if a single index lesion cannot be identified and sampled; otherwise allowed if a representative lesion can be biopsied.
3. 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
Primary outcome measure(s)
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. — Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease) 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)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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