Molecular characterization of intratumor heterogeneity of different breast cancer subtypes and their microenvironment using multiomic platforms and patient-derived models: a prospective pilot study
Early-stage ER-positive, HER2-negative luminal high-risk breast cancer, HER2-positive breast cancer, triple-negative breast cancer treated with standard of care neoadjuvant therapies.
This is a prospective, single-centre, observational translational pilot study in patients with early-stage breast cancer receiving standard-of-care neoadjuvant treatment. Eligible patients with triple-negative, HER2-positive, or ER-positive/HER2-negative high-risk luminal breast cancer are enrolled at Institut Jules Bordet. The study does not alter treatment decisions. Tumour tissue and blood samples are collected prospectively before treatment, at surgery, and optionally during treatment; additional longitudinal blood samples are collected during follow-up. Collected samples include FFPE tissue, frozen tumour tissue, fresh tumour tissue, plasma, serum, peripheral blood mononuclear cells, and one germline reference blood sample. Multiomic analyses include bulk DNA and RNA sequencing, DNA methylation profiling, single-cell sequencing, spatial transcriptomics, multiplex imaging, and circulating tumour DNA analyses. Fresh tumour samples may also be used to generate patient-derived models. Molecular, cellular, spatial, and immune profiling data are integrated with clinicopathological and outcome data to study intratumour heterogeneity, tumour microenvironment composition, systemic immune response, treatment response, and disease outcome.
1. Adult patients aged 18 years or older 2. Histologically confirmed early-stage breast cancer planned for neoadjuvant systemic treatment at Institut Jules Bordet 3. Breast cancer subtype eligible for this observational translational study: 3.1. Triple-negative breast cancer, or 3.2. HER2-positive breast cancer, 3.3. ER-positive/HER2-negative high-risk luminal breast cancer 4. No evidence of metastatic disease at study entry 5. Willing and able to provide written informed consent for collection of tissue, blood, and clinical data 6. Availability of baseline and planned surgical material, with optional on-treatment biopsy where feasible 7. For the TNBC expansion cohort: tumor size at least T1c with node-positive disease, or tumor size at least T2, or otherwise eligible for neoadjuvant pembrolizumab plus chemotherapy according to KEYNOTE-522 and institutional multidisciplinary tumor board decision
1. Patients not meeting the inclusion criteria 2. Metastatic breast cancer at study entry 3. Refusal or inability to provide informed consent 4. Inability to provide the required research samples according to protocol procedures