Newsletter 2

Find out how our Meet our See what’s In patient-focused new been going research might academic and on in our this impact future industry Seminar and breast cancer collaborators Workshop Issue patients Series newsletter Issue 2 Director’s Message Autumn 2014 As we come towards the end of a highly successful first year, I am delighted with the progress that has been made on all fronts within BREAST-PREDICT, in terms of research advances, publications, educational events, funding successes, and clinical trials. We have already yielded a healthy stream of Over the last few months, in addition to our leveraging the significant investment placed publications, including notable outputs in ongoing seminar series, we have had a in us by the Irish Cancer Society. several top-tier cancer journals. We have selection of informative and well-attended Finally, my happiness with progress is made great strides in terms of incorporating workshops covering the areas of molecular somewhat tempered by the sad passing of a new epidemiological component to imaging, quantitative pharmacology and the late Professor John Fitzpatrick, Head of ongoing clinical studies, as well as made systems biology, familial breast cancer and Research at the Irish Cancer Society. significant progress in terms of patient other aspects of translational cancer Professor Fitzpatrick’s vision in terms of the accrual on translational substudies. research. Such events are key to raising our establishment of Collaborative Cancer profile within the national and international In particular, we ended our first year with a Research Centres paved the way for our community, while also providing an very productive and engaging meeting with continued efforts to find better ways of important training dimension for our five members of our international Scientific personalising breast cancer treatment. His students and research staff. Advisory Board on 5th September 2014, passionate voice and effusive support for highlighting our initial research Several BREAST-PREDICT investigators what we were planning to create will stay achievements and future plans. Their valued have been successful in winning significant with me as we progress forward. input will be instrumental in guiding us additional new grant awards (totalling in Professor William Gallagher towards future success. excess of €4 million), thereby already Director, BREAST-PREDICT The BREAST-PREDICT team First Scientific Advisory Board meeting The Irish Cancer Society Collaborative Cancer Research Centre (CCRC) BREAST-PREDICT now directly employs 13 PhD researchers, 11 Postdoctoral researchers, 3 Research Assistants, a Research Nurse, a Clinical Research Associate, a Translational Research Co-ordinator, a Senior Lecturer and a Centre Co-ordinator. The research team is led by 20 of the top Principal Investigators in Ireland in the breast cancer field, and comprises an expanding network of affiliated researchers. Overall, the BREAST-PREDICT CCRC comprises a team of over 50 talented researchers working together with the goal of UCD, Sept 2014 improving the lives of breast cancer patients in Ireland. The BREAST-PREDICT team met with members of their Scientific Advisory Board (SAB) on the 5th of September 2014 in UCD. The purpose of this meeting was to allow the group to highlight their research achievements in the first year of the Centre, and to benefit from the expertise of the Scientific Advisory Board in guiding future plans. Five of the seven board members attended this first meeting, including Prof. Robert Clarke of Georgetown University, an expert in the area of endocrine resistance in breast cancer; Dr. Garret Hampton, Head of Oncology Michelle Lowry Amelia Smith Louise Walsh Dr. Sonja Khan PhD student PhD student PhD student Postdoctoral Fellow Biomarker Development in Genentech; Prof. Mats Lambe, an expert in Medical Epidemiology from the Karolinska Institute in Sweden; Prof. Richard Kennedy, a Consultant Medical Oncologist from Queen’s University Belfast (QUB), and Prof. Liam Murray, an expert in Public Health and Epidemiology, also from QUB. The BREAST-PREDICT team spent the morning presenting their research to the SAB, followed by a poster session at lunchtime where PhD students and Girish Mallya Udupi Laura Ivers Dr. Laoighse Mulrane Aoife Carr postdoctoral fellows discussed their work. The afternoon was given over to an Research Engineer Research Assistant Postdoctoral Fellow PhD student engaging discussion on progress, with specific feedback given by the SAB on each Welcome to our new members research area, in addition to general advice on future directions. Both the SAB and the BREAST-PREDICT team enjoyed the meeting, and we are looking forward to renewed discussions at the end of Year 2. In the first year, the BREAST-PREDICT team have published 12 primary Research research articles and 8 review articles, Highlights from these publications, and details of some ongoing work, are described below. Aspirin may help halt the spread of breast cancer ADAM8: A promising therapeutic target in BREAST-PREDICT researchers from Trinity College Dublin have triple-negative breast cancer discovered that women who had During the last decade, considerable progress has been prescribed aspirin regularly been made in the treatment of breast cancer, before being diagnosed with especially in hormone receptor-positive and breast cancer are less likely to Her2-positive cancer. Thus, a wide array of have cancer that spread to the therapeutic options are available which specifically lymph nodes than women who were not on prescription aspirin. These target these breast cancer subtypes, such as women are also less likely to die from their breast cancer. The study of tamoxifen for hormone receptor-positive cancers, Irish patients, published in the journal Cancer Research, analysed and Herceptin for Her2-positive cancers. In records from the National Cancer Registry Ireland (NCRI), and contrast, little progress on targted therapies has been made in the prescription data from the General Medical Service (GMS) pharmacy treatment of breast tumours which lack estrogen receptors, claims database. progesterone receptors and Her2, known as triple-negative breast 'Our findings suggest that aspirin could play a role in reducing cancer (TNBC). This tumour type is generally treated with mortality from breast cancer by preventing the cancer spreading to conventional approaches such as surgery, radiotherapy and nearby lymph nodes', says Dr Ian Barron, lead author on the study. 'We chemotherapy, and there is an urgent need for new targeted analysed data from 2,796 women with stage I-III breast cancer. We treatments for TNBC patients. found that those women prescribed aspirin in the years immediately BREAST-PREDICT Investigator Prof. Joe Duffy, together with prior to their breast cancer diagnosis were statistically significantly postdoctoral fellow Dr. Patricia McGowan, both based at St. less likely to present with a lymph node-positive breast cancer than Vincent’s University Hospital/UCD, were involved in a recent large non-users. The association was strongest among women prescribed multicentre collaborative study involving investigators in Boston, aspirin regularly and women prescribed higher aspirin doses. We now Marburg, Nantes and London as well as Dublin. The study, published need to establish how and why this is the case'. in the journal EMBO Molecular Medicine, reported that a protease Prof. Kathleen Bennett, co-author on the study, said; 'Our study was known as ADAM8 was expressed at particularly high levels in TNBC, observational and these results do not mean that women should start and, furthermore, that high levels of ADAM8 were associated with taking aspirin as a precautionary measure. Aspirin can have serious side poor outcome in these patients. Moreover, reducing the levels of of effects. We still need to identify exactly how aspirin may prevent ADAM8 in a mouse model of TNBC resulted in decreased tumour breast cancer from spreading to the lymph nodes; which women, or growth. Based on these findings, targeting ADAM8 would appear to types of breast cancer, are most likely to benefit from taking aspirin; as be a promising approach for the treatment of patients with TNBC. well as what the optimum doses might be.’ Supporting this, the paper also presents evidence that mice with Research to help answer these questions is ongoing under the TNBC, when treated with a monoclonal antibody therapy targeting BREAST-PREDICT programme. In addition to population-based ADAM8, had a reduced risk of the tumour spreading. Further studies, researchers will carry out pre-clinical studies, which aim to research is ongoing to assess the potential of this therapy, with the decipher the mechanism through which aspirin mediates these effects. ultimate goal of developing a new targeted drug for TNBC patients. BREAST-PREDICT researchers work together to overcome resistance to Her2 targeted therapies. Prof. Lorraine About one quarter of all women diagnosed with breast cancer BREAST-PREDICT O’Driscoll, a member will be Her2-positive, meaning that their tumour cells have researchers Dr. of the high levels of the Her2 protein. This type of breast cancer is Norma O’Donovan BREAST-PREDICT generally quite aggressive. However, the recent development and Prof. John research team based of targeted therapies, which work by directly targeting and Crown, based in in Trinity College killing cells with high levels of the Her2 protein, has DCU and St. Dublin, made a dramatically improved

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