Developing Breast (Cancer) Organoids

Overview

Currently, only a few validated biomarkers and models exist guiding or predicting treatment response for specific patient groups. Therefore, a patient-tailored clinical model needs to be developed to address tumour heterogeneity and thereby guide treatment selection on an individualized level. Organoids are patient-derived aggregates that grow in 3D and maintain self- renewal pluripotency and lineage-specific differentiation. Therefore, in contrast with conventional cell lines, they are thought to sustain patient heterogeneity and characteristics and are consequently already in use for drug response screening. This now offers the opportunity to investigate if the primary patient breast cancer organoid platform reflects disease progression, treatment response and relapse in patients with different clinical breast cancer subtypes. Goal: To develop a living biobank from prospective patient-derived breast cancer tissue. The questions we will address are: 1. Do patient-derived breast cancer organoids retain the clinical behaviour and characteristics of the primary patient tumour? 2. Can BC organoids be used to derive prognostic and predictive biomarkers to inform treatment decisions? 3. Can the investigators utilize BC organoids to discover novel actionable targets and combination treatments for therapeutic intervention for breast cancer patients? 4. Can BC organoids be used to discover mechanisms of treatment resistance and relapse?

The investigators will select patients with a diagnosis of breast cancer who undergo breast surgery. Patients will be asked informed consent for the use of a small (0,2-1 cm3) sample of the excised breast tumour and the collection of a blood sample (6ml)for whole-exome sequencing (WES) to compare the genetic profile of the patients with the organoids and the patient biopsy. The patients will not undergo any additional treatment or procedure in addition to the planned routine procedure for the surgical resection of their primary breast tumour. Patient will undergo standard diagnostic procedures and treatment according to the Dutch breast cancer surgery guidelines. After surgery, the pathologist will provide -after pathological diagnosis- rest (tumour) tissue from the resection to the lab. This material will then be used to develop breast cancer organoids. As part of the routine surgical procedure, 6 ml of blood will be collected. Participation in this study does not lead to additional actions other than reading the patient information and signing the informed consent. Therefore, participation does not change the patient's treatment or outcome.