Clinical research on breast cancer

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. Find out more about the Cambridge Breast 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 current open trials for breast cancer coordinated by the Cambridge Cancer Trials Centre (last updated 31 January 2014). 

Trial name Trial description Contact
ABSC Study: Adult Breast Stem Cells Study ABSC Study: Adult Breast Stem Cells Study Prof Carlos Caldas
AZD9496 – Oral SERD Phase I

Oral SERD Phase I - A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women with Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer

Dr Richard Baird

The principal objective of this pilot study is to examine the use of a prototype acquisition sequence in terms of its ability to distinguish breast lesions on DCE-MR images enabling pharmacokinetic modelling (Ktrans and Ve mapping) and assessing implementation in routine clinical practice.

To evaluate a new pulse sequence that allows improved temporal and spatial resolution of DCE acquistitions through the use of k-space veiw sharing. A standard DCE breast imaging sequence (VIBRANT) has been modified to support the Time Resolved Imaging of Contrast KineticS (TRICKS) k-space acquisition strategy previously employed for time-resolved MR angiography. This technique allows a four-fold improvement in temporal resolution, which itis hypothesized will lead to more robust and clinically useful DCE-based imaging metrics for breast tumours.

Prof Fiona Gilbert
CANC - 3490 OLYMPIA 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 breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy Dr Jean Abraham
DETECT Indentification and Classification of Circulating Tumour Cells and Circulating Nucleic Acid in patients with Metastatic Breast Cancer Prof Carlos Caldas
IMPORT HIGH Randomised trial testing dose escalated intensity modulated radiotherapy in women with higher than average local tumour recurrence risk after breast conservation surgery and appropriate systemic therapy for early breast cancer Dr Charlotte Coles
PAKT A  Phase II, randomized, placebo-controlled study of the AKT inhibitor AZD5363 in combination with paclitaxel in triple-negative advanced or metastatic breast cancer  Dr Richard Baird
Poseidon Phase I/prospective randomised phase II trial Of the Safety and Efficacy of tamoxifen in combination with alpha Isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alONe in hormone receptor positive, HER2 negative, metastatic breast cancer patients with prior exposure to endocrine treatment  Dr Richard Baird
RADICAL A single arm phase IIa study (with combination safety run-in) to assess the safety and efficacy of AZD4547 in combination with either anastrozole or letrozole in ER positive breast cancer patients who have progressed on treatment with anastrozole or letrozole Dr Richard Baird
TRANS-NEO Prospective molecular profiling of tumour tissue and isolation of circulating nucleic acids from patients receiving neo-adjuvant treatment for early breast cancer Prof Carlos Caldas

If you would like further information about how to take part in any of the clinical trials listed here that are open to recruitment, 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