Clinical research on breast cancer

Staff

University of Cambridge
Department of Oncology
Cambridge University Hospitals NHS Foundation Trust
Department of Oncology
Cambridge University Hospitals NHS Foundation Trust
Department of Oncology

Every year over 45,000 new cases of breast cancer are diagnosed in the UK. About 75% of the women are cured but 25% still die of the disease. Breast cancer research in Cambridge is aiming to increase the survival rate through...

  • Large-scale population studies to determine which genes are responsible for causing breast cancer
  • Genetic barcoding to identify different cancer types and to help develop specific treatments
  • Testing new treatments on patients in clinical trials

We are conducting, and have completed, several trials in order to demonstrate the value of neo-adjuvant studies as a platform to qualify new drugs and drug combinations, and improve drug development. We have also designed several clinical trials to optimise the use of molecularly targeted therapies.

We have worked on improving delivery of radiotherapy for better loco-regional control with less toxicity. Results of trials led from Cambridge have already facilitated changes of UK practice in breast radiotherapy, for instance titanium clip placement to allow accurate tumour bed localisation and the extension of the use of Intensity Modulated Radiation Treatment.

Cambridge Breast Unit

Cambridge has established a ‘one-stop’ clinic, the Cambridge Breast Unit, for rapid diagnosis of breast cancer. The diagnostic accuracy of the triple assessment (clinical examination, imaging and biopsy) is 99.6%. Nine-year survival rates of breast cancer patients treated at Addenbrookes Hospital is 84%, compared with a regional average of 78%. Around half of patients diagnosed with breast cancer at the clinic enter a clinical trial run by the Cambridge Breast Cancer Research Unit.

Cambridge Breast Cancer Research Unit

The Cambridge Breast Cancer Research Unit has collected over 20,000 tumour samples from breast cancer patients. This large diverse collection of tissue samples will be essential in the development and testing of new ways to diagnose the different types of breast cancer.

Barcoding breast cancer – METABRIC
A major collaborative research project analysing the genetic barcodes of 2,000 breast cancer samples, with 5–15 years follow-up, has identified 10 different types of breast cancer. Each has distinct molecular characteristics and different survival rates, which will now inform different treatment options. The results of this research are being used to develop new tests to diagnose different breast cancer types, which will then enable each patient to be given the most effective course of treatment. Cambridge is also helping to unravel the full genetic sequence for breast cancer, as part of an international initiative to identify the genetic blueprint of 50 cancers.

Clinical tool to predict breast cancer risk - BOADICEA
One of the significant successes of the Cambridge Cancer Centre has been to establish the BOADICEA web-based BRCA1 and BRCA2 carrier probability prediction model as a clinical tool for familial cancer clinical worldwide. In the next few years we expect to have identified multiple loci that modify the breast and ovarian cancer risks in BRAC1 and BRCA2 deleterious mutation carriers. These variants will be incorporated into the model. Ultimately one of the questions we want to answer is what are the characteristics, in terms of penetrance and population frequencies, of confirmed cancer susceptibility alleles.

Clinical tool to inform prognosis and treatment of breast cancer – PREDICT
PREDICT is a breast cancer prognosis and treatment web-based tool. It has been developed on the basis of clinical research data collected in the UK to aid multi-disciplinary teams in the management of women with early stage breast cancer, in particular whether a patient would benefit from adjuvant chemotherapy. PREDICT is now the prognostic/predictive tool of choice for the Cambridge Breast Unit and is widely used throughout the NHS and beyond to assess the ideal course of treatment post-surgery.

Breast cancer treatment trial – IMPORT
This is a breast radiotherapy trial which has resulted in Intensity Modulated and Image Guided radiotherapy being introduced into more UK centres as a standard of care.

Response to hormone therapy
We have identified how the oestrogen receptor-cistrome in primary tumours modulates response to hormone therapy. We demonstrated differential oestrogen receptor (ER) binding events in primary breast cancer (a first ever) and revealed a role for the pioneer factor FoxA1 as a crucial ER regulatory protein in drug resistant contexts, providing the impetus to develop therapeutic FoxA1 inhibitors. 

Improved monitoring of therapy response
Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. We have demonstrated the clear advantages of using circulating tumour DNA over other tests as a biomarker for monitoring treatment response and disease progression in patients with metastatic disease. Specifically, we have developed a new approach, sequencing of cancer exomes in plasma, to study a series of patients who have developed resistance to chemotherapy, hormone therapy and Trastuzumab, with the aim of identifying potential causing mutations.

Current open trials in Cambridge

The table below lists the current open trials for breast cancer coordinated by the Cambridge Cancer Trials Centre (last updated February 2018).   If you would like further information about how to take part in any of the clinical trials listed here, please talk to your cancer specialist as patients usually need to be referred by their doctor

 

Cambridge Cancer Trials Centre contact for breast cancer trials: Dr Helena Earl

Titlesort descending Trial description Contact name Trial end date Trial start date
Add-Aspirin Trial - Breast A phase III, double blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours Dr Luke Hughes-Davies 11 Dec 2020 21 Dec 2015
CORE A randomised trial of conventional care versus radioablation (stereotactic body radiotherapy) for extracranial metastases Dr Susan Harden 31 Oct 2019 29 Mar 2018
FAST-Forward FAST Forward is a randomised clinical trial testing a 1-week course of curative whole breast radiotherapy against a standard 3-week schedule in terms of local cancer control and late adverse effects in patients with early breast cancer. The lymphatic RT sub-study an extension to the FAST-Forward trial, which maintains its original design but whose entry is now restricted to patients prescribed radiotherapy to level I-III axilla and/or level IV axilla (supraclavicular fossa (SCF)) in addition to the breast/chest wall area. Dr Charlotte Coles 1 Feb 2022 12 Mar 2012
Neo-RT Pre-operative breast intensity modulated radiotherapy in patients receiving neo-adjuvant hormonal treatment for breast cancer – a feasibility study Dr Charlotte Coles 1 Sep 2024 4 Dec 2017
Olympia / MA.36 A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy Dr Jean Abraham 23 Jan 2019 23 Jan 2015
OPTIMA Optimal Personalised Treatment of early breast cancer using Multiparameter Analysis Dr Luke Hughes-Davies 31 Oct 2020 25 Oct 2012
PARTNER Randomised, phase II/III, 3 stage trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in breast cancer patients with TNBC and/or gBRCA Dr Jean Abraham 31 Mar 2021 12 May 2016
plasmaMATCH A multiple parallel cohort, non-randomised, open label, multi-centre phase IIa clinical trial aiming to provide proof of principle efficacy for designated targeted therapies in patients with advanced breast cancer where the targetable mutation is identified through ctDNA screening Dr Richard Baird 31 Dec 2018 11 Apr 2017
POSNOC POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes Professor John Benson 30 Sep 2018 8 Aug 2014
PRIMETIME Post-operative avoidance of radiotherapy in minimal risk women: patient selection using biomarkers Dr Charlotte Coles 31 Dec 2021 18 May 2017
Quartus Quantification of breast radiotheraphy associated in late toxicity using novel ultrasound techniques Dr Charlotte Coles 31 Jan 2019 13 May 2016