4th IMPAKT Breast Cancer Conference

Dr Sherene Loi talks to ecancer about the heterogeneity of breast cancer tumours at IMPAKT 2012 in Brussels, May 2012. Technology now allows for the understanding of the cancer genome down to the base pair of certain types of cancer. In small tumour breast cancer, less than 2cm, the tumours have multiple ‘clones’ and these ‘clones’ drive the growth of the tumour. Treatment of one tumour can be the reason for relapses as another tumour can then proliferate. Dr Loi also discusses PI3 kinase, which is essential for cell growth but highly irregular in breast cancer and especially in triple negative breast cancer where no targeted therapies yet exist.

Prof Tak talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012, about his insights in to the basis for molecular therapy. Prof Tak uses an analogy of oncogenes being the 'horses' pulling the 'cart' of cancer. Prof Tak points out that while it looks promising to target any one of the hundreds of oncogenes which cause cancer, they essentially all result in the same 2 or 3 metabolic pathways so perhaps we should be investigating the metabolism processes instead, as a potential for a 'catch-all' treatment.

A new analysis may help doctors identify breast cancer patients who will benefit from treatment with the immune suppressant drug everolimus, said French researchers at the 4th IMPAKT Breast Cancer Conference in Brussels, Belgium. Everolimus is currently used as an immunosuppressant to prevent patients rejecting transplanted organs and in the treatment of renal cell cancer. Research is also being conducted into the drug’s use in other cancers, including breast cancer. Dr Thomas Bachelot, from Centre Leon Berard in Lyon and colleagues analyzed data from the TAMRAD study, published two years ago

Prof Helleday talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012, about novel therapies for triple negative breast cancer including the use of 6-mercaptopurine, previously not used in this group of patients. The plan is to tackle cells which have been resistant to cisplatin or PARP inhibitors; Prof Helleday discusses studies underway.

Prof Finn talks to ecancer at at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012, about the results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for firstline treatment of ER+/HER2- advanced breast cancer. The new compound has the potential to be a standard of care in this setting, if a phase 3 study is successful, and also has promise in the adjuvant setting.

Prof Mitch Dowsett talks to ecancer about important papers presented at IMPAKT 2012 in Brussels, May 2012, on endocrine therapy, drug resistance, cell cycling and combination therapy. Prof Dowsett discusses findings on everolimus, data from the BOLERO-2 study, which was presented by Prof Jose Baselga, and the outcomes from a phase 2 study involving CDK inhibitors.

Prof Michail Ignatiadis talks to ecancer about neoadjuvant therapy and pathological complete response (PCR) at IMPAKT 2012 in Brussels, May 2012. The study conducted looks at whether or not neoadjuvant therapy should be used in order to reach pathological complete response. Results have shown that this can occur after commonly used therapies. Data shows that patients with HER2 amplified and triple negative tumours have excellent response when receiving chemotherapy before surgery. After treatment, biopsies can be used to determine tumour type and its sensitivity to chemotherapy for future record. The most important finding in the study was that the immune response module had a signficantly higher probability of complete pathological response.

Prof Ellis talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012, about the molecular complexity of endocrine therapy resistance and the potential of next generation sequencing to facilitate drug development.

Prof Martine Piccart talks to ecancer about heterogeneity of breast cancer tumours, advancements in technology and the future of treating breast cancer at IMPAKT 2012 in Brussels, May 2012. IMPAKT 2012 focused on the latest developments in translational research, teaching young oncologists on how to treat patients in the coming years and especially on the heterogeneity of tumours. New technologies hold the potential for understanding the evolution of breast cancer and the differences between primary tumours and metastases. With HER+ tumours, each type of tumour, slow growing and highly proliferating, hold very specific molecular characteristics that can potentially unlock new understandings of the disease through the patient's immune system and the microenvironment.

Dr Lewis Cantley talks to ecancer about PI3K and the development of inhibitors for clinical use at IMPAKT 2012 in Brussels, May 2012. PI3K, phosphoinosititde 3-kinase is a signalling pathway that controls growth. PI3K is the most frequently mutated gene in breast cancer. Currently, there are 20 inhibitors in phase 1 or 2 trials. Dr Cantley mentions that there has been good response in phase 1 trials, but while many patients had very good reactions, others did not respond. The message to take away from this is that doctors should be more aggressive in doing mutational analyses and, more importantly, that this information become more accessible for retroactive analysis for other targetable mutations.

Dr Larry Norton talks to ecancer about drug resistance and targeting pathways at IMPAKT 2012 in Brussels, May 2012. Dr Norton states that cancer research is at the point where the understanding of cancer is enough to start driving towards eradication of the disease. While numerous pathways have been identified, there are only about ten critical pathways. Dr Norton is currently working on applying mathematics to the problem of using more than one drug in a complementary system. The difficulty in intelligent dosing with targeted therapy is finding a balance in treatment. If treated too intensely, resistance will develop quicker, therefore treatment needs to be slow paced in order to overcome and, in some cases, prevent resistance.

Prof Jorge Reis-Filho talks to ecancer about molecularly characterising triple negative breast cancer at IMPAKT 2012 in Brussels, May 2012. At the molecular level, triple negative breast cancer is not a single disease. There are a larger number of heterogeneous tumours, which means that this disease cannot be analysed in the same way as other types of breast cancer. The differences between diseases are the biological starting point for testing different therapeutic agents against triple negative breast cancer. The different subtypes of tumours can each respond differently to strategies, but will give prognostic signatures that will point to a quick and clear prognosis. However, there are complications with what type of prognostic signatures can be used in triple negative cases.

Prof Gunter Von Minckwitz talks to ecancer about assessing neoadjuvant therapy in breast cancer and recent developments at IMPAKT 2012 in Brussels, May 2012. Recent developments have allowed patients to benefit by receiving better treatment through more accurate prognostics on the subtype of their tumour. There are now a series of trials that show an increase of complete pathological response in patients with HER2+ tumours.

Prof Giuseppe Curigliano talks to ecancer about the heterogeneity of tumours and the challenges of biomarker development at IMPAKT 2012 in Brussels, May 2012. Specific mutations like PI3K mutation or p54 mutation provide targetable mutations for drug development; however, mutations found in the primary tumour are not the same as the metastatic tumour. Once a tumour is present, significant changes occur in the body and to the immune system when the tumour metastases treatment needs to focus on the microenvironment. Research conducted on future treatments involves CTCs, bone cells and tools to quickly characterise tumours.

Prof Fabrice Andre talks to ecancer about identifying patients with a high risk of recurrence at IMPAKT 2012 in Brussels, May 2012. The importance of identifying high risk patients is not just discovering which are the most susceptible to relapse, but to avoid giving a patient a therapy that will have a low effect as well. Prof Andre notes that by using protein based and prognostic biomarkers, the best possible therapy with the lowest risk of relapse, can be identified. The second challenge that Prof Andre addresses is how to bridge the gap between research settings and clinical practice.

Prof Daniel Hays talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012 about which criteria should be met before the implementation of whole genome arrays in clinical practice.

Prof Swanton talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012, about variations within the tumour itself and the implications for new types of personalized medicine.

Dr Prat talks to ecancer at the IMProving care And Knowledge through Translational research (IMPAKT) meeting in Brussels, May 2012. Gene expression tests currently available are not an option for most of the world due to cost and assay turn around time, so Dr Prat led a team looking at gene expresssion data across 5 independent studies to try to improve pathology based biomarkers. The study found that progesterone receptor-positive cells acted as a biomarker identifying luminal A tumours, thus enabling the identification of the sub-group of patients who may not need adjuvant systemic chemotherapy. Gene expression data combined with pathological data improves the management of certain breast cancer patients; however issues such as cost and logistics need to be overcome.

Prof Alastair Thompson talks to ecancer about the effects of metformin and AMP kinase on the survival rates in breast cancer at IMPAKT 2012 in Brussels, May 2012. Metformin, normally used as an anti-diabetes drug, has shown large effects on breast cancer. Prof Thompson notes that patients who take metformin for their diabetes have lower instance of cancer, improved outcome with chemotherapy and higher survival rate. The molecular mechanisms of metformin work through AMP kinase though research does not show if it has a direct effect on the cancer or the feeding of cancer cells. Metformin is known to reduce proliferation in cancer cells in women. Overall, the potential effect of metformin is a 5 to 10 % reduction in events and recurrence with a substantial increase in survival, as well as evidence from human studies showing that metformin works on all breast cancers, including triple negative cancer, and a number of other cancers.