Breast Cancer Research Projects Overview
Ongoing breast cancer research projects focusing on biomarker validation, new team initiatives, and imaging advancements are detailed. Notable efforts include the investigation of triple-negative breast cancer markers, benign breast disease progression markers, ER+ and HER2+ biomarkers, and breast cancer imaging with blood biomarkers. Collaborative teams are striving to improve screening accuracy, prioritize high-risk individuals, and advance diagnostic methods for better patient outcomes.
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Triple Negative Breast Cancer Team Project Lead: Karen Andeson (ASU) Collaborators: Li/Lampe (FHCRC), Marks (Duke), Zangar (PNNL) Status: Manuscript submitted Aim: 1. Validation of blood-based biomarkers specific to triple- negative breast cancer Next steps: 1. Optimize assays by transitioning to a meso-scale platform to improve their performance 2. Explore opportunities to evaluate markers in the context of imaging or use in high risk clinics
Benign Breast Disease (BBD) Team Project Lead: Paul Engstrom (Fox Chase) Jeff Marks (Duke) Collaborators: Godwin (Kansas), Stark (Geisinger) Status: Continuing Aims: 1. Validation of tissue-based biomarkers that distinguish BBD that is high risk/likely to progress vs. those that will not progress 2. Assemble a reference set of BBD cases that progressed and BBD controls. Accomplishments: 1. Reference set assembled from Geisinger and Northwestern: 101 cases and 196 matched controls 2. 11 markers prioritized for testing at Duke (complete) and KU (on-going) Core Funds Request: Leader: Jeff Marks (Duke) Submit centralized pathology review data and image capture to the DMCC (VSIMS) and deliver slides to NCI Frederick Complete staining of slides for the remaining markers at KU
Identification of biomarkers for ER+ and HER2+ breast cancer Lead: Christopher Li (FHCRC) Collaborators: Anderson/LaBaer (ASU), Marks (Duke), Paulovich (FHCRC) Status: Approved Aims: 1. Validation of blood-based biomarkers specific to ER+ breast cancer 2. Validation of blood-based biomarkers specific to HER2+ breast cancer Potential Clinical Applications: 1. Biomarkers to inform timing of subsequent screening among women with a negative mammogram 2. Biomarkers to inform continuation of mammographic screening among women 75-79 years of age 3. Identify high risk women who should be prioritized for screening in areas with limited resources/access to mammography Sample Sets: EDRN reference set, preclinical samples from WHI and CHS
Breast Cancer Imaging and Blood Biomarkers Leads: Jeffrey Marks (Duke), John Heine (Moffitt) Collaborators: Tang (Creatv MicroTech) Status: Proposal needs to be revised and resubmitted to the EC Aims: 1. Create repositories of breast images linked to blood specimens for combined analyses 2. Improve predictive accuracy of mammography toward reducing the biopsy rate Cohorts: BIRADS 4 or 5 patients in the diagnostic setting 1. Retrospective cohort of ~1000 images (full field digital)/blood (primarily from Duke) for training of image analysis 2. Prospective cohort of ~1000 images (tomosynthesis)/ blood (freshly collected) from Moffitt and Duke Issues: Justification for retrospective cohort, need to specify biomarkers to be tested, rationale for including BI-RADS 4C and 5
Avatar Mice-to-Human Breast Cancer Biomarkers Lead: Amanda Paulovich (FHCRC) Collaborators: Lewis (Baylor), Rodland (PNNL) Status: Conditionally approved Aim: 1. Identify blood-based biomarkers for use in conjunction with mammography to improve sensitivity and specificity Approach: 1. 58 breast PDX models (Lewis) and others from PDX consortium detect human proteins in mouse plasma using mass spec (LC-MS/MS with targeted LC-MS), evaluate for utility as early detection markers 2. Build immuno-MRM assays for top candidates Set-aside project: 1. Add glycoproteomics at PNNL (N-glycopeptide capture) Issues: 1. Minor comments that are addressable
Summary of Breast Cancer Projects Ongoing or new? Project Lead Status Ongoing Triple negative Karen Anderson Manuscript submitted, clarify next steps for clinical translation Ongoing Benign breast disease Jeff Marks Will submit a core funds request New ER+ and HER2+ Chris Li Approved New Imaging/blood Jeff Marks Revise and resubmit New Avatar mice Mandy Paulovich Conditionally approved
