IMPAKT 2013

Prof Perou talks to ecancer reporter Peter Goodwin about the Cancer Genome Atlas; working to target drugs and improve treatment by forming a comprehensive picture of breast cancer biology. They also discuss an overview of biomarkers, pathways and inhibitors, drugs in the pipeline for PI3 Kinase and looking at ER positive, HER2 negative cancers. Potential therapeutic advances in triple negative breast cancers are also covered.

ecancer reporter Peter Goodwin talks to Dr Navin at the 2013 IMPAKT conference in Brussels about the new technology of single cell sequencing. Blood tests allow the sampling of CTCs and thus the genome of any primary and metastatic tumours; this then allows the progress of a tumour to be monitored and it's repsonse to certain therapies. There is also potential for very early detection of tumours, and in the future a yearly test for early stage tumours which could lead to a huge reduction in deaths from cancer.

Prof Caldas talks to ecancer reporter Peter Goodwin at IMPAKT 2013, May 2nd, in Brussels, about the sub types of breast cancer looked at in the METABRIC study on the molecular stratification of breast cancer; and the latest analysis of that data.

ecancer reporter Peter Goodwin talks to Dr Rosanna Lau about the contribution of analytical, pre-analytical and intra-tumoural heterogeneity to variance in gene expression measurements from human breast cancers. Her new study has revealed the clearest picture yet of precisely how much measurement variation influences gene expression profiles of breast cancer. The results show, for the first time, which gene expression measurements may benefit from pooling of biopsies from a single tumour. These findings represent an important step toward allowing doctors to more precisely tailor an individual’s treatment to a detailed analysis of their tumour’s gene expression.

orld-leading epidemiologist Prof Jack Cuzick talks to ecancer about his paper in the Lancet confirming that selective estrogen receptor modulators (SERMs) are both effective and safe for preventing breast cancer in women who are at high risk of the disease but who are not ill. There has been caution about using tamoxifen and raloxifene (both SERMs) following scare stories in the US: Prof Cuzick's meta analysis addreses this and brings hope of avoiding a third of breast cancers.

ecancer reporter Peter Goodwin talks to Dr Yanina Dockx at the 2013 IMPAKT meeting in Brussels. Aberrant activation of the PI3K-Akt-mTOR pathway is an important driver of resistance to HER2 targeted therapies and is involved in glucose homeostasis. 18F-FDG-PET has been proposed for early response assessment for targeted therapies, but knowledge on the effects of blocking this pathway on FDG uptake dynamics is limited. The study investigated the effect of pharmacological PI3K-Akt-mTOR blockade on in vitro FDG uptake in HER2 breast cancer cells resistant to trastuzumab. Blockade of PI3K-Akt-mTOR in trastuzumab resistant HER2 breast cancer was found to affect in vitro 18F-FDG uptake in transient and opposite ways, depending on the pharmacological target and duration of treatment. Therefore, further validation is necessary to elucidate the cellular mechanisms involved in tracer uptake prior to routine clinical use for early response assessment.

Prof Piccart talks to ecancertv at the 2013 IMPAKT meeting in Brussels about her assessment of genetic alterations in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer from the BOLERO-2 trial by next-generation sequencing. Prof Piccart also discusses the types of genetic alterations, the types of test, the potential for more subtypes of breast cancer, and the clinical implications of genomic and proteomic assessment.

ecancer reporter Peter Goodwin talks to Dr Sara Hurvitz at IMPAKT 2013 in Brussels. What does the future hold for PI3K/AKT/mTOR inhibitors in breast cancer?

ecancer reporter Peter Goodwin talks to Dr Thordur Oskarsson of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) at IMPAKT 2013 in Brussels. They discuss how the extracellular matrix proteins of stem cell niches promote breast cancer metastasis, and what implications this might have for future treatment.

ecancer reporter Peter Goodwin talks to Dr Carey at the 2013 IMPAKT conference in Brussels about redesigning drug trials in the genomic era. They discuss the different trial options available including neoadjuvant trials.

ecancer reporter Peter Goodwin talks to Dr Jarząb at the 2013 IMPAKT conference in Brussels about a new study providing reassurance that the variability in different cell types with different patterns of gene expression should not be a barrier to using gene expression tests to help tailor cancer treatments to individual patients. The researchers performed gene expression profiling on their 78 samples using oligonucleotide microarrays. Overall, they found that the gene expression profiles of the cores were variable, and in at least 5 patients this heterogeneity was substantial. However, when they analysed a number of multi-gene signatures selected from previous studies, this heterogeneity was considerably less significant. The gene sets differed in their variance between biopsies, the authors found. The most pronounced heterogeneity was observed in immune response-related genes, while the least heterogeneous were the classifiers based on genes selected by advanced bioinformatical methods from both cell culture experiments and patient tissues.

ecancer reporter Peter Goodwin talks to Dr Willard-Gallo at the 2013 IMPAKT conference in Brussels about IDing immune response in breast cancer, helping to asses prognosis. CD4 T cells are critical regulators of immune responses but their functional role in breast cancer is relatively unknown. The goal of the study was to produce an image of CD4 T cells infiltrating breast tumors (TIL) using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. The identification of CD4 T cells as a new key immune element in breast cancer, linked with organized immunity and associated with a higher response rate to chemotherapy and/or excellent long-term clinical outcome, suggests that their presence in some tumours is an important prognostic factor.

ecancer reporter Peter Goodwin talks to Dr Mills at the 2013 IMPAKT conference in Brussels about the MD Anderson's current 'Moon Shot' programme looking at the genetics of triple negative breast cancer to take preventative action such as prophlyactic surgery. They also discuss new assays that look for defects in the function of BRCA1 and BRCA2 genes and the promise of PARP inhibitors in patients with abnormalities in BRCA1 and BRCA 2 genes.

ecancer reporter Peter Goodwin talks to Dr Ana Vivancos at the 2013 IMPAKT meeting in Brussels about her research in to enrolement strategies in Phase I clinical trials. Dr Vivancos offers advice on the assessment of different mutations and what biomarkers are currently being looked at. Being able to more properly profile the molecular characetirstics of a tumour can lead to improvement of clinical trials and the best therapy for the patient. Dr Vivancos encourages clinicians to integrate genomics in to their every day practice.

ecancer reporter Peter Goodwin talks to Dr Wildiers at the 2013 IMPAKT conference in Brussels about the latest treatments for HER 2 positive breast cancer, for example combining antiobodies with cytoxics, eg TDM-1.

ecancer reporter Peter Goodwin talks to Dr Sestak at the 2013 IMPAKT conference in Brussels about a new analysis which has provided a comprehensive comparison of scores designed to predict which women with oestrogen-receptor positive breast cancer are at high risk of recurrence beyond five years after diagnosis, and may benefit from prolonged endocrine treatment. The ATAC trial included nearly 10,000 women who were treated with surgery followed by five years of treatment with the drugs anastrozole, tamoxifen or a combination of both. Of these 1,125 from the monotherapy arms (tamoxifen, anastrozole) were included in the transATAC study. The five scores being compared were: Clinical Treatment Score, which includes information on the patient’s disease and treatments so far; IHC4 score, which characterises the presence of cell surface markers on cancer cells; The Oncotype Dx Recurrence Score; The PAM50 Risk of Recurrence Score; The Breast Cancer Index score. The results showed that the clinical treatment score alone was the best for predicting late recurrence, the researchers report. The components of this score include some that are already widely used by doctors, such as whether the cancer has spread to sentinel lymph nodes, the tumour size and grade. Among the other tests, the PAM50 risk of recurrence score and the Breast Cancer Index score added the most significant prognostic value between years 5 and 10 after diagnosis.