Enabling the Study of Metabolism in Breast Cancer Through Collection of Fresh-tissue Biopsies
Enabling the Study of Metabolism in Breast Cancer Through Collection of Fresh-tissue Biopsies
This study aims to evaluate how breast cancer cells metabolise nutrients in order to grow.
 Patients enrolled into this study will undergo a research biopsy that will aim to collect up
 to 4 cores of tumour tissue. These tissues will then be used in translational research to
 analyse how specific pro-tumorigenic events change breast cancer cell metabolism (compared to
 healthy cell metabolism).
Comprehensive analysis linking breast tumour subtypes and their genetic profile with tumour
 metabolism are required. Traditional model systems are inadequate for this purpose.

 1. In vitro models do not represent a true tumour environment and are a subject of
 prolonged adaptation to artificial cell culture conditions.

 2. There is a need for in vivo and ex vivo models representing breast cancer diversity and
 tumour environment that can be used for predicting and testing the personalised
 therapies.

 Metabolic analysis of fresh tissues (by metabolomics and Mass Spectrometry Imaging (MSI)) and
 tissues grown as patient derived xenograft models in vivo should reveal the unperturbed
 relationships between genetic profiles of tumour cells, tumour microenvironment and metabolic
 profiles of tumours. These relationships should provide new targets for metabolism-based
 therapies. The experimental systems required to perform this research require fresh breast
 cancer biopsies.

 ENSEMBLE is a prospective multi-centre cohort study that aims to address these issues. Fresh
 breast tumour tissue will be collected from consented female participants diagnosed with
 invasive breast cancer, for translational research. Up to 240 participants will be enrolled
 over a 36-month period and clinical follow-up data will be collected for up to 5 years. Study
 participants will undergo a "research biopsy" (core biopsy) for translational research that
 aims to collect up to four cores. The procedure is the same as the standard of care
 percutaneous core needle biopsy that the patient will have to inform their diagnosis,
 however, as it is an additional procedure, it is called a "research biopsy". Wherever
 possible biopsy samples will be taken from the operative specimen at the time of primary
 surgery however, where neo-adjuvant therapy is planned in a patient's care plan, these
 patients will undergo a research percutaneous biopsy prior to their surgery, performed either
 using image-guidance or as a clinical biopsy.

 Collected tumour material will be divided: a portion will immediately be frozen in liquid
 nitrogen, and a portion will be kept fresh. The material will be transported to the primary
 receiving laboratory at the Francis Crick Institute where part of the sample will be
 immediately engrafted into immune-deficient mice to create a patient-derived xenograft (PDX)
 model. The remaining primary samples and samples from PDXs will be used for genomic,
 metabolomic and other biochemical analyses.

 Information about participant demographics, medical history and tumour characteristics will
 be collected at registration. Participants may be followed up for up to 5 years for clinical
 outcome data and to clarify information about medical history
Inclusion Criteria:

 -  Histological diagnosis of newly diagnosed breast cancer

 -  Known ER and HER2 receptor status

 -  Tumour diameter ≥1cm on imaging

 -  Female

 -  Age 18 or above

 -  Written informed consent

 Exclusion Criteria:

 -  Previously treated invasive breast cancer

 -  Primary systemic therapy for breast cancer prior to biopsy

 -  Oestrogen replacement therapy (HRT) within 14 days of biopsy in ER-positive tumours

 -  Pregnancy or breastfeeding

 -  Not considered suitable by clinical team