Breast Cancer

Personalised Breast Cancer Programme – choosing the right treatment for each patient by mapping their tumour DNA and RNA.

The PARTNER/PARTNERING prospective clinical trials – PARPi and further novel drugs in TNBC and/or BRCA+ BC patients.

Personalised Breast Cancer Programme (PBCP)

The pioneering Cambridge based Personalised Breast Cancer Programme (PBCP), led by the Department of Oncology’s Professor Carlos Caldas and Dr Jean Abraham, was set up to both advance research and to benefit patients currently undergoing treatment. The PBCP is using advances in genetics to map each patient’s tumour DNA, in order to identify which of the breast cancer disease groups they belong to. Sequencing the tumour DNA identifies a pattern of mutations which acts like a barcode for the patient’s cancer. This barcode enables doctors to choose the right treatment and also helps early identification of when a tumour is coming back, as tumour cells release their DNA which can be detected in a blood test known as a liquid biopsy.

How it works:

  • All breast cancer patients have two genetic DNA codes, the germline code inherited from their parents and the damaged code in their tumour.
  • Breast cancer patients in Cambridge have their full germline and tumour codes sequenced, with the results sent to their doctor within 12 weeks.
  • The germline code shows whether they inherited mutations in BRCA1, BRCA2 genes, which increases their risk of both breast and ovarian cancer and has implications for their family members.
  • The tumour code enables researchers to catalogue all the mutations in the cancer cells, allowing them to identify which breast cancer disease group they belong to and predict which treatment they will respond best to.

The pilot phase of the PBCP began in November 2016 as a collaboration between Cancer Research UK and Addenbrooke’s Charitable Trust, to determine whether a patient’s genetic test results could be returned to their medical team within 12 weeks. Over 250 patients from Addenbrooke’s Breast Cancer Unit took part in the pilot, becoming the first NHS breast cancer patients to have whole genome sequencing of their tumour, in a clinically impactful timeframe, as part of their routine treatment.

Cancer Research UK has awarded over £1m in funding for the next phase of the programme, with further funding to come from The Mark Foundation for Cancer Research, a US-based philanthropic organisation. This new funding will allow the programme to be rolled out to a further 2,000 patients over the next 4 years, initially at a number of sites in the East of England later in 2019, with further sites across the UK added in 2020/2021.

CRUK Cambridge Centre article on the PBCP

PARTNER/PARTNERING: Clinical Investigator

Dr Jean Abraham

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The PARTNER/PARTNERING is a trial for women with early triple negative (TNBC) and BRCA mutation positive (BRCA+BC) breast cancer. Neoadjuvant chemotherapy is commonly used to shrink tumours prior to surgical intervention. Improving the effectiveness of pre-operative, neoadjuvant chemotherapy for patients with TNBC and/or BRCA+BC is important since the amount of residual tumour at surgery is closely associated with clinical outcome.

The PARTNER trial is investigating the use of Olaparib, in the pre-operative, neoadjuvant setting. Olaparib blocks the activity of an enzyme called poly ADP ribose polymerase (PARP) that repairs DNA. Cancer cells with mutations in BRCA1/2 are thought to have a unique vulnerability to Olaparib since they rely on PARP to repair their DNA and enable them to continue dividing. The PARTNER trial tests if Olaparib is safe to add to platinum-based, pre-operative, neoadjuvant chemotherapy for TNBC and/or BRCA+BC and whether it improves the effectiveness of platinum chemotherapy alone.

Clinical trial registration

The PARTNERING component of the trial seeks to establish if the addition of further novel drugs (Olaparib, Wee1 inhibitor and PDL1 inhibitor) improves the response at surgery in those patients who are poor responders to the initial treatment within the PARTNER trial.

These two trials link to MFICM research by including elements of all 4 data streams and their integration

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The Mark Foundation Institute for Integrated Cancer Medicine (MFICM) at the University of Cambridge aims to revolutionise cancer care by affecting patients along their treatment pathway.

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