Over the past several years our multidisciplinary research team has been dedicated to discovering and validating candidate early detection biomarkers for breast and ovary cancers. We are now in an ideal position to lead an EDRN CVC for several reasons: 1. We have lists of promising breast and ovary cancer early detection biomarkers that have been evaluated in Phase 1 to early Phase 3 validation studies that warrant further investigation in Phase 3 studies;2. We have developed considerable expertise in the design, conduct, analysis, and interpretation of cancer biomarker discovery and validation studies;3. Over the course of four work we have developed or gained access to a large number of high quality well-characterized breast and ovary cancer sample repositories that we are willing to share with EDRN;and 4. We have a long history of leading and supporting collaborative projects that have involved shared samples, and we have procedures in place to facilitate the processing and tracking of specimen requests. Herein we propose a new prospective collection of preclinical specimens from breast cancer cases and controls which is unique in that it will include detailed mammography information. We also propose a series of primarily Phase 3 validation studies. For breast cancer we will conduct a Phase 3 study beginning in Year 1 (Study 1) and then plan to design a series of Phase 2 and 3 studies in Years 4-5 (Study 5) as candidates from our work and others in EDRN mature. The primary specific aim of Study 1 is to conduct a second screen of promising candidates identified in a large discovery project using preclinical samples, and to then validate the top candidates in an independent set of preclinical samples from WHI. For ovary cancer we propose a consecutive series of three Phase 3 studies over Years 1-3. Several ovary cancer biomarkers have been validated, but none achieve clinically useful performance on their own. Thus, Study 2 is a Phase 3 validation aimed at validating and refining two- and four-marker algorithms using serial preclinical samples from the PLCO trial. Study 3 will further validate specific screening decision rules in preclinical serial samples from the UKCTOCS trial. Based on Studies 2 and 3, Study 4 will validate ovary cancer markers and screening decision rules in an independent set of WHI serial preclinical samples, a setting in which no ovary cancer screening occurred.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1-SRLB-3 (M1))
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Patriotis, Christos F
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Fred Hutchinson Cancer Research Center
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Garrison, Carly B; Lastwika, Kristin J; Zhang, Yuzheng et al. (2017) Proteomic Analysis, Immune Dysregulation, and Pathway Interconnections with Obesity. J Proteome Res 16:274-287
Buas, Matthew F; Gu, Haiwei; Djukovic, Danijel et al. (2016) Identification of novel candidate plasma metabolite biomarkers for distinguishing serous ovarian carcinoma and benign serous ovarian tumors. Gynecol Oncol 140:138-44
Wu, Jing; Yin, Haidi; Zhu, Jianhui et al. (2015) Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study. PLoS One 10:e0121112
Urban, Nicole; Hawley, Sarah; Janes, Holly et al. (2015) Identifying post-menopausal women at elevated risk for epithelial ovarian cancer. Gynecol Oncol 139:253-60
Buas, Matthew F; Rho, Jung-hyun; Chai, Xiaoyu et al. (2015) Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study. Breast Cancer Res Treat 153:445-54
Pepe, Margaret S; Li, Christopher I; Feng, Ziding (2015) Improving the quality of biomarker discovery research: the right samples and enough of them. Cancer Epidemiol Biomarkers Prev 24:944-50
Schummer, Michèl; Thorpe, Jason; Giraldez, Maria D et al. (2015) Evaluating Serum Markers for Hormone Receptor-Negative Breast Cancer. PLoS One 10:e0142911
Karlan, Beth Y; Thorpe, Jason; Watabayashi, Kate et al. (2014) Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women. Cancer Epidemiol Biomarkers Prev 23:1383-93
Pepe, Margaret S; Janes, Holly; Li, Christopher I (2014) Net risk reclassification p values: valid or misleading? J Natl Cancer Inst 106:dju041
Brauer, Heather Ann; D'Arcy, Monica; Libby, Tanya E et al. (2014) Dermcidin expression is associated with disease progression and survival among breast cancer patients. Breast Cancer Res Treat 144:299-306

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