# A unique approach combining avatar mice and targeted mass spectrometry to identify blood biomarkers for early detection of breast cancer

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $187,791

## Abstract

Project Summary/Abstract
 Tens of millions of women undergo population-based screening for breast cancer by mammography. De-
spite the life-saving potential of early detection, screening guidelines for mammography are controversial and
continue to evolve. At issue are the specificity of mammography for distinguishing benign vs cancerous le-
sions, the sensitivity of mammography in some patient populations (e.g. women with dense breasts), and con-
cerns regarding over-diagnosis (e.g. some ductal carcinoma in situ). Our ultimate clinical aim is to develop a
blood test for early detection of breast cancer that can be used in conjunction with mammography to improve
sensitivity and specificity during screening, and thus have enormous clinical impact by detecting treatable can-
cers missed by mammography (reducing mortality) and by avoiding unnecessary invasive procedures for be-
nign or non-life-threatening disease.
 Despite considerable effort, attempts to identify blood-based screening biomarkers for early detection of
breast cancer have failed, due to technological and methodological limitations. Clearly new approaches are
warranted. We are proposing a completely novel strategy, based on the initial discovery of candidate bi-
omarkers in the plasma of “avatar mice” (harboring early passage human breast cancer xenografts), and fol-
lowed by biomarker triage and validation using a novel biomarker pipeline based on a targeted form of mass
spectrometry (MS), multiple reaction monitoring (MRM). If successful, this study could provide a road map for
applying this general approach to other cancer sites, beyond breast cancer.
 Briefly, candidate circulating biomarkers identified in the avatar mouse plasma will be verified in the plasma
from the human patients and prioritized for further testing based on integrative proteo-genomic analyses using
large breast cancer datasets generated by NCI genomic and proteomic consortia (TCGA and CPTAC). A nov-
el, multiplex MRM-based assay will be developed and analytically validated (according to established fit-for-
purpose guidelines) to quantify up to 50-100 prioritized biomarker candidates. Candidate biomarkers will be
evaluated in an existing, strongly unbiased collection of plasma samples in which plasmas were collected prior
to biopsy, compliant with PRoBE study design criteria, under an SOP from women with undiagnosed mammo-
graphic lesions. Performance of the candidate biomarkers will initially be assessed in a training set (100 cas-
es, 100 controls) to verify which candidates show a mean difference in plasma levels between cases vs con-
trols, and to test the possibility of building a multiple marker prediction model. Subsequently, individual candi-
date biomarkers (as well as a potential multiple marker prediction model) will be assessed in an independent
validation set (150 cases, 150 controls) to estimate the sensitivity and specificity of the markers/panel.

## Key facts

- **NIH application ID:** 10462864
- **Project number:** 3U01CA214172-05S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Michael T. Lewis
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $187,791
- **Award type:** 3
- **Project period:** 2016-09-19 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462864

## Citation

> US National Institutes of Health, RePORTER application 10462864, A unique approach combining avatar mice and targeted mass spectrometry to identify blood biomarkers for early detection of breast cancer (3U01CA214172-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462864. Licensed CC0.

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