Fred Hutchinson Cancer Center
United States
Fred Hutchinson Breast Cancer Clinical Validation Center
There remain clear clinical and public health needs to improve the early detection of breast cancer. While mammography is an effective tool, there are issues with respect to optimizing its use and performance, and despite widespread screening breast cancer remains the 2nd most common cause of cancer related death among U.S. women. Through the current EDRN Clinical Validation Center (CVC) led by Dr. Li we have validated 15 candidate biomarkers through a series of Phase 2 and Phase 3 validation studies that involved successive series of three independent sets of preclinical samples. Outside of EDRN funding, Dr. Partridge has led the development of novel strategies to improve breast cancer detection based on quantitative markers derived from screening MRIs in high-risk women and application of artificial intelligence (AI) approaches in collaboration with Microsoft. Our overarching goal is to conduct Phase 2 and 3 validation studies of bloodbased biomarkers and imaging strategies that will be integrated and jointly assessed in a Phase 4 validation study. Supporting this goal we propose the following 4 projects: Project 1: Phase 3 validation of early detection biomarkers for ER+ breast cancer; Project 2: Phase 2 and 3 validation of protein biomarkers for the early detection of breast cancer discovered using a mass spectrometry-based platform; Project 3: Phase 3 validation of quantitative markers and AI algorithms applied to MRI screening exams for the early detection of breast cancer in women at high risk; and Project 4: Phase 4 validation of blood-based biomarkers and imaging algorithms for the early detection of breast cancer. Additionally, we will provide biospecimens and expertise to support high quality PRoBE compliant EDRN discovery and validation studies across several cancer types. With the combined expertise of our multidisciplinary team of investigators and our engagement with key commercial partners, this CVC will both lead well-justified, rigorously designed validation studies and provide abundant resources to EDRN. Given the strength of our biomarker candidates, the sets of biospecimens that will be used, the study designs employed, and the clearly delineated clinical applications proposed, we anticipate that this work will yield near-term clinical impact.
Publications
- Buas MF, Li CI, Anderson GL, Pepe MS. Recommendation to use exact P-values in biomarker discovery research in place of approximate P-values. Cancer epidemiology. 2018 Oct;56:83-89. Epub 2018 Aug 10. PMID: 30099328
- Wu J, Yin H, Zhu J, Buckanovich RJ, Thorpe JD, Dai J, Urban N, Lubman DM. Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study. PloS one. 2015 Mar 23;10(3):e0121112. doi: 10.1371/journal.pone.0121112. eCollection 2015. PMID: 25799488
- Buas MF, Drescher CW, Urban N, Li CI, Bettcher L, Hait NC, Moysich KB, Odunsi K, Raftery D, Yan L. Quantitative global lipidomics analysis of patients with ovarian cancer versus benign adnexal mass. Scientific reports. 2021 Sep 13;11(1):18156. PMID: 34518593
- Trentham-Dietz A, Corley DA, Del Vecchio NJ, Greenlee RT, Haas JS, Hubbard RA, Hughes AE, Kim JJ, Kobrin S, Li CI, Meza R, Neslund-Dudas CM, Tiro JA. Data gaps and opportunities for modeling cancer health equity. Journal of the National Cancer Institute. Monographs. 2023 Nov 8;2023(62):246-254. PMID: 37947335
- Li CI, Mirus JE, Zhang Y, Ramirez AB, Ladd JJ, Prentice RL, McIntosh MW, Hanash SM, Lampe PD. Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women's Health Initiative observational study. Breast cancer research and treatment. 2012 Sep;135(2):611-8. Epub 2012 Aug 19. PMID: 22903690
- Bresalier RS, Grady WM, Markowitz SD, Nielsen HJ, Batra SK, Lampe PD. Biomarkers for Early Detection of Colorectal Cancer: The Early Detection Research Network, a Framework for Clinical Translation. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Dec;29(12):2431-2440. Epub 2020 Apr 16. PMID: 32299850
- Rho JH, Ladd JJ, Li CI, Potter JD, Zhang Y, Shelley D, Shibata D, Coppola D, Yamada H, Toyoda H, Tada T, Kumada T, Brenner DE, Hanash SM, Lampe PD. Protein and glycomic plasma markers for early detection of adenoma and colon cancer. Gut. 2018 Mar;67(3):473-484. Epub 2016 Nov 7. PMID: 27821646
- Böhm J, Pianka F, Stüttgen N, Rho J, Gigic B, Zhang Y, Habermann N, Schrotz-King P, Abbenhardt-Martin C, Zielske L, Lampe PD, Ulrich A, Diener MK, Ulrich CM. Discovery of novel plasma proteins as biomarkers for the development of incisional hernias after midline incision in patients with colorectal cancer: The ColoCare study. Surgery. 2017 Mar;161(3):808-817. Epub 2016 Oct 13. PMID: 27745870
- Buas MF, Rho JH, Chai X, Zhang Y, Lampe PD, Li CI. Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study. Breast cancer research and treatment. 2015 Sep;153(2):445-54. Epub 2015 Aug 30. PMID: 26319120
- Brauer HA, D'Arcy M, Libby TE, Thompson HJ, Yasui YY, Hamajima N, Li CI, Troester MA, Lampe PD. Dermcidin expression is associated with disease progression and survival among breast cancer patients. Breast cancer research and treatment. 2014 Apr;144(2):299-306. Epub 2014 Feb 22. PMID: 24562771
- Garrison CB, Lastwika KJ, Zhang Y, Li CI, Lampe PD. Proteomic Analysis, Immune Dysregulation, and Pathway Interconnections with Obesity. Journal of proteome research. 2017 Jan 6;16(1):274-287. Epub 2016 Nov 14. PMID: 27769113
- Schummer M, Drescher C, Forrest R, Gough S, Thorpe J, Hellström I, Hellström KE, Urban N. Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125. Gynecologic oncology. 2012 Apr;125(1):65-9. Epub 2011 Dec 7. PMID: 22155417
- Ladd JJ, Chao T, Johnson MM, Qiu J, Chin A, Israel R, Pitteri SJ, Mao J, Wu M, Amon LM, McIntosh M, Li C, Prentice R, Disis N, Hanash S. Autoantibody signatures involving glycolysis and splicesome proteins precede a diagnosis of breast cancer among postmenopausal women. Cancer research. 2013 Mar 1;73(5):1502-13. Epub 2012 Dec 26. PMID: 23269276
- Schummer M, Thorpe J, Giraldez MD, Bergan L, Tewari M, Urban N. Evaluating Serum Markers for Hormone Receptor-Negative Breast Cancer. PloS one. 2015 Nov 13;10(11):e0142911. doi: 10.1371/journal.pone.0142911. eCollection 2015. PMID: 26565788
- Lech Pedersen N, Mertz Petersen M, Ladd JJ, Lampe PD, Bresalier RS, Davis GJ, Demuth C, Jensen SØ, Andersen CL, Ferm L, Christensen IJ, Nielsen HJ. Development of blood-based biomarker tests for early detection of colorectal neoplasia: Influence of blood collection timing and handling procedures. Clinica chimica acta; international journal of clinical chemistry. 2020 Aug;507:39-53. Epub 2020 Apr 6. PMID: 32272156
- Buas MF, Gu H, Djukovic D, Zhu J, Drescher CW, Urban N, Raftery D, Li CI. Identification of novel candidate plasma metabolite biomarkers for distinguishing serous ovarian carcinoma and benign serous ovarian tumors. Gynecologic oncology. 2016 Jan;140(1):138-44. Epub 2015 Oct 30. PMID: 26521694
- Drescher CW, Shah C, Thorpe J, O'Briant K, Anderson GL, Berg CD, Urban N, McIntosh MW. Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 Jan 20;31(3):387-92. Epub 2012 Dec 17. PMID: 23248253
- Miller CP, Thorpe JD, Kortum AN, Coy CM, Cheng WY, Ou Yang TH, Anastassiou D, Beatty JD, Urban ND, Blau CA. JAK2 expression is associated with tumor-infiltrating lymphocytes and improved breast cancer outcomes: implications for evaluating JAK2 inhibitors. Cancer immunology research. 2014 Apr;2(4):301-6. Epub 2014 Jan 15. PMID: 24764577
- Karlan BY, Thorpe J, Watabayashi K, Drescher CW, Palomares M, Daly MB, Paley P, Hillard P, Andersen MR, Anderson G, Drapkin R, Urban N. Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014 Jul;23(7):1383-93. Epub 2014 May 1. PMID: 24789859
- Drescher CW, Hawley S, Thorpe JD, Marticke S, McIntosh M, Gambhir SS, Urban N. Impact of screening test performance and cost on mortality reduction and cost-effectiveness of multimodal ovarian cancer screening. Cancer prevention research (Philadelphia, Pa.). 2012 Aug;5(8):1015-24. Epub 2012 Jul 2. PMID: 22750949
- Urban N, Thorpe JD, Bergan LA, Forrest RM, Kampani AV, Scholler N, O'Briant KC, Anderson GL, Cramer DW, Berg CD, McIntosh MW, Hartge P, Drescher CW. Potential role of HE4 in multimodal screening for epithelial ovarian cancer. Journal of the National Cancer Institute. 2011 Nov 2;103(21):1630-4. Epub 2011 Sep 14. PMID: 21917606
- Urban N, Thorpe J, Karlan BY, McIntosh MW, Palomares MR, Daly MB, Paley P, Drescher CW. Interpretation of single and serial measures of HE4 and CA125 in asymptomatic women at high risk for ovarian cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012 Nov;21(11):2087-94. Epub 2012 Sep 7. PMID: 22962406
- Urban N. Designing early detection programs for ovarian cancer. Annals of oncology : official journal of the European Society for Medical Oncology. 2011 Dec;22 Suppl 8(Suppl 8):viii6-viii18. PMID: 22180403
- Urban N, Hawley S, Janes H, Karlan BY, Berg CD, Drescher CW, Manson JE, Palomares MR, Daly MB, Wactawski-Wende J, O'Sullivan MJ, Thorpe J, Robinson RD, Lane D, Li CI, Anderson GL. Identifying post-menopausal women at elevated risk for epithelial ovarian cancer. Gynecologic oncology. 2015 Nov;139(2):253-60. Epub 2015 Sep 3. PMID: 26343159
- Zhao W, Fitzgibbon M, Bergan L, Clegg N, Crispin D, Mills GB, McIntosh M. Identifying Abundant Immunotherapy and Other Targets in Solid Tumors: Integrating RNA-seq and Mass Spectrometry Proteomics Data Sets. Cancer journal (Sudbury, Mass.). 2017 Mar-Apr;23(2):108-114. PMID: 28410298
- Pepe MS, Li CI, Feng Z. Improving the quality of biomarker discovery research: the right samples and enough of them. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 Jun;24(6):944-50. Epub 2015 Apr 2. PMID: 25837819
- Kunihiro AG, Sarrett SM, Lastwika KJ, Solan JL, Pisarenko T, Keinänen O, Rodriguez C, Taverne LR, Fitzpatrick AL, Li CI, Houghton AM, Zeglis BM, Lampe PD. CD133 as a Biomarker for an Autoantibody-to-ImmunoPET Paradigm for the Early Detection of Small Cell Lung Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 Nov;63(11):1701-1707. Epub 2022 Apr 28. PMID: 35483965
- Pepe MS, Janes H, Li CI. Net risk reclassification p values: valid or misleading? Journal of the National Cancer Institute. 2014 Apr;106(4):dju041. Epub 2014 Mar 28. PMID: 24681599
- Oviedo F, Kazerouni AS, Liznerski P, Xu Y, Hirano M, Vandermeulen RA, Kloft M, Blum E, Alessio AM, Li CI, Weeks WB, Dodhia R, Lavista Ferres JM, Rahbar H, Partridge SC. Cancer Detection in Breast MRI Screening via Explainable AI Anomaly Detection. Radiology. 2025 Jul;316(1):e241629. PMID: 40662973