Breast Cancer, Hereditary Diseases
Conditions
Brief summary
UPTIDER is a prospective, interventional, non-Investigational Medicinal Product (non-IMP), non-commercial, single centre post-mortem tissue donation program for metastatic breast cancer patients or patients with a germline pathogenic variant with a moderate to high lifetime risk of breast cancer and at least one malignancy at time of death. The overarching objective of UPTIDER is (i) to unravel metastatic breast cancer evolution, biology, heterogeneity and treatment resistance and (ii) to assess pathogenicity and tumour biology in hereditary cancer syndromes with a high lifetime risk of breast cancer; both through extensive post-mortem multi-level and multi-region sample analysis.
Interventions
PROCEDUREBlood draw
Blood draw at inclusion
PROCEDUREPost-mortem tissue collection
Sample collection (both liquids, tumour tissue and non-tumour tissue) during post-mortem research autopsy
Sponsors
KU Leuven
Universiteit Antwerpen
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Signature of informed consent by the subject. * Metastatic breast cancer, or hereditary cancer syndrome with a moderate to high lifetime risk of breast cancer, for which the patient is treated/followed in UZ Leuven or treated in another hospital and referred to UZ Leuven specifically for the trial. Additional inclusion criteria for the different substudies: * Pilot phase: no additional inclusion criteria. * ILC substudy: histologically confirmed history of ILC. * IBC substudy: history of IBC, fulfilling the following criteria described by Dawood et al: rapid onset of breast erythema, oedema and/or peau d'orange and/or warm breast with or without an underlying palpable mass, duration of history of no more than 6 months, erythema occupying at least one-third of the breast and pathological confirmation of invasive carcinoma. * Hereditary cancer syndrome substudy: confirmed presence of a germline mutation known to be associated with a moderate to high lifetime risk of BC (e.g. known pathogenic variants in the genes BRCA1/2, CHEK2, TP53, PALB2) and presence of at least one malignant lesion at time of inclusion (of any origin) . * Other substudies: no additional inclusion criteria.
Exclusion criteria
* Presence of a transmissible disease that can form a risk to the health of researchers or others handling the body or patient samples. This includes but is not limited to the following infectious diseases: human immunodeficiency virus (HIV), active hepatitis C virus (HCV), encephalitis of unknown cause, Creutzfeldt-Jakob disease, rabies, active malaria, active tuberculosis, active SARS-CoV-2 infection. * Presence of any factors that could logistically or organizationally impede the study or the performance of sampling within a reasonable post-mortem time frame. This includes but is not limited to: residence of the subject at a faraway distance from the UZ Leuven hospital; residence of the subject on territory outside of Belgium; impossibility to notify the clinician confirming the death and the researchers within a reasonable time frame in case of death. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of samples with sufficient quality of RNA extracted | During autopsy | RNA integrity number (RIN) |
| Percentage of patients consenting to participate in the pilot phase | Baseline | Should be equal to or above 50% |
| Median time elapsed between moment of death and start of the autopsy | During autopsy | Should be equal to or less than 12h |
| Median time elapsed between collection of first and last sample | During autopsy | Should be equal to or less than 8h |
| Percentage of metastatic organs sampled | During autopsy | Should be equal to or more than 75% |
| Percentage of samples with sufficient quality of DNA extracted | During autopsy | A260/A280 ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of T cell exhaustion | During autopsy | RNA sequencing |
| Number of mutations in each tumor lesion | During autopsy | Whole exome sequencing |
| Type of mutations in each tumor lesion | During autopsy | Whole exome sequencing |
| Percentage of Tumour Infiltrating Lymphocytes (TILs) | During autopsy | Standard histopathological review |
| Concordance between TILs and clinical response to treatment | During autopsy | Standard histopathological review |
Countries
Belgium
Contacts
Primary ContactGiuseppe Floris, MD PhD
Backup ContactChristine Desmedt, PhD
Outcome results
None listed