Molecular Analysis of Residual Breast Cancer

PROJECT SUMMARY Breast cancer is a leading cause of cancer deathPMIDAccording to the WHObreast cancer incidence rosebetweenandwithM global diagnoses inMore thanwomen died from breast cancer in the U SinResidual disease is important because breast cancer patients with positive margins have a high risk of recurrence and disease specific mortalitySome studies indicate a surprisingly high risk from positive marginspatients with positive margins have a higher risk of recurrence than patients who have micrometastases tolymph nodesThe elevated risk from positive margins continues to persist even in an era where lumpectomy patients are treated with radiotherapy and systemic therapiesIn factthe increased risk from positive margins is not reduced by additional chemo or a radiation boostThese findings underscore the continued importance of identifying positive marginsespecially when clinical trial data will be used to evaluate emerging therapies or compare treatment efficaciesImproving the diagnosis and treatment of breast cancer depends on clinical trialswhich must account for confounding clinical variables like residual diseaseEvidence based medicine depends on the quality of the underlying data that are used to evaluate therapeutic options and perform comparative efficacy studiesUnfortunatelyexisting tests are not reliable enough to accurately and reproducibly detect residual diseaseInaccurate tests contribute to confusion and conflicting trial resultsThis goal of this project is to establish an improved test for residual breast cancerThis work builds on extensive development and validation of a panel of biomarkers that distinguishes tumors from healthy samplesThis project will continue our transition from discovery platforms to a technology that is already widely used in clinical labsImproved testing would improve clinical trials by identifying high risk patientsallow researchers to ask fundamental questions about breast cancer treatmentsand compare treatment efficacies PROJECT NARRATIVE Detection of minimal residual disease for liquid tumors has undergone two revolutionsfrom microscopy to flow cytometryand then from flow cytometry to nucleic acid testsEach advance transformed clinical managementMeanwhiledetection of residual disease for solid tumors continues to rely on microscopic sectioningwhich is not an ideal way to hunt for residual diseaseThis project will establish a research test that uses nucleic acids to detect residual tumor along the surface of surgical breast cancer specimens