THE LATEST IN BREAST CANCER RESEARCH Causes ….pptx

What’s Positive about Triple Negative Breast Cancer?Julie R. Gralow, M.D.Jill Professor Endowed Professor of Breast CancerDirector, Breast Medical OncologySeattle Cancer Care AllianceUniversity of Washington School of MedicineFred Hutchinson Cancer Research CenterBreast Cancer: Classic Prognostic and Predictive FactorsHER-2 +20-25% of Breast CancerEstrogen Receptor (ER) + 75% of Breast CancerTriple Negative Breast CancerNo expression of ER, PR, ER215% of breast cancersAggressive, higher recurrence ratesChemotherapy is currently main treatment optionMore common in:Young womenAfrican AmericansHispanicsBRCA1+ (80%)Racial Distribution of Triple Negative Breast CancerStead LA, et al, Breast Cancer Research 11:R18, 2009Timing of Recurrence in Triple Negative Breast Cancer vs. Other SubtypesDent et al. Clin Can Res 2007; 13: 4429Gene Expression Profiling in Breast CancerOver the last decade, gene expression profiling has given us insights into the biological complexity of breast tumorsClinically applicable gene expression-based assays have been and are being developed for prediction of prognosis and/or treatment benefitMolecular Classification of Breast Cancer: Breast Cancer is NOT One Disease!The Cancer Genome Atlas Network. Nature 490, 2012“Heat Map”Normal Breast–likeBasal Luminal ALuminal BHER-2+Red dots: Genes are “turned up” in cancer cells compared to normal cellsIndividual genesIndividual patientsBasal SubtypeLow expression of luminal and HER2 gene clustersTypically ER-, PR-, and HER-2-negative, but up to 30 percent discordanceHigh expression of proliferation cluster genes, virtually always high grade, widespread genomic instabilityHigh expression of EGFR and unique basal cluster genes (basal epithelial cytokeratins 5, 14, and 17)p53 mutations commonOther receptors and pathways can be altered (c-kit, c-met, RAS-MAPK, mTOR/PI3K)Strong association with cancers in BRCA1 mutation carriers (over 80 percent basal-like)Associated with DNA repair defectsPARP1 commonly incr