# Multiregional imaging phenotypes and molecular correlates of aggressive versus indolent breast cancer

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $485,193

## Abstract

ABSTRACT
The goal of this research is to develop and validate prognostic imaging biomarkers for breast cancer.
A major challenge in the management of breast cancer is distinguishing patients with indolent disease
from those with aggressive lethal disease at diagnosis. Currently, there are no reliable biomarkers to
distinguish these groups on an individual level. Consequently, all patients with breast cancer receive
adjuvant therapies, but not all benefit equally. This one-size-fits-all approach causes overtreatment,
leading to morbidity and mortality. The need for reliable biomarkers is highlighted by the randomized
TAILORx trial, which identified a small group of low-risk breast cancer patients who had very low
rates of recurrence without chemotherapy, based on the 21-gene Oncotype Dx assay. Unfortunately,
a majority (67%) of patients fell in the intermediate-risk range according to the genomic assay, and
uncertainty still remains regarding the need for chemotherapy among these patients. Clearly, better
biomarkers are needed to improve prognostication and patient stratification in breast cancer. Built on
extensive preliminary data, we hypothesize that imaging characteristics reflect underlying tumor
pathophysiology, and that image-based phenotyping of both tumor and parenchyma will provide
much improved accuracy for recurrence prediction. To test this hypothesis, we propose to: (1)
develop and improve methods to explicitly quantify multiregional MRI phenotypes including those of
intratumoral subregion and parenchyma, and systematically assess their reproducibility; (2) develop a
prognostic imaging signature using a large retrospective cohort of >1000 patients curated by the
Stanford Oncoshare Project, and validate it in the prospective multi-center I-SPY 1 cohort; (3)
construct a radiogenomic signature to perform additional testing of its prognostic value in 13 public
gene expression cohorts of >5000 breast cancer patients. To further improve prognostication, we will
build a multifactorial model that integrates imaging with clinical and genomic markers. This research
will advance the quantitative imaging field by moving beyond traditional gross-tumor features and
incorporating additional parenchymal and intratumoral imaging characteristics. If successful, it will
provide much needed, rigorously validated imaging biomarkers for breast cancer, which can be
further tested for clinical utility in prospective trials. Ultimately, such biomarkers can be used to stratify
patients and guide individualized therapy, by allowing clinicians to avoid overtreatment of indolent
disease and intensify treatment in women with aggressive disease.

## Key facts

- **NIH application ID:** 9857570
- **Project number:** 5R01CA222512-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ruijiang Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,193
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857570

## Citation

> US National Institutes of Health, RePORTER application 9857570, Multiregional imaging phenotypes and molecular correlates of aggressive versus indolent breast cancer (5R01CA222512-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857570. Licensed CC0.

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