# Stromal contributions to breast carcinogenesis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $758,543

## Abstract

ABSTRACT
The human breast is a highly organized, complex organ that consists of an epithelial tissue surrounded by
stroma that regulates its proliferation, differentiation, and survival. Stroma is responsible for sustaining normal
breast tissue structure and function via a variety of signaling mechanisms that control and regulate normal
processes and suppress malignant transformation. The role of stroma in breast tumor initiation, progression,
and responsiveness to treatment as well as potential utility for targeted therapies has been widely discussed in
recent reviews. While cancer tissue stroma has been widely explored, the evidence of stromal contributions to
early stages of carcinogenesis is extremely limited. To fill these gaps, we propose a conceptually and
methodologically novel investigation that will focus on benign breast disease (BBD) and high mammographic
breast density (MBD), strong risk factors both independently associated with increased breast cancer (BCa)
risk, which presents a unique opportunity for studying early changes in the breast and elucidating underlying
molecular mechanisms. The study will be conducted by an interdisciplinary team of experts in BCa
epidemiology, breast pathology/image analysis, BCa biology, and biostatistics, with a history of long and
productive collaboration. We will use data and breast biopsy samples from three established prospective
cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Women’s Health Repository) to address the
following aims: (1) prospectively examine associations of reproductive risk factors (e.g., parity, age at first birth)
with expression of stromal markers (αSMA, FAP, MMP14, TNC, and S100A6) in benign biopsy samples from
cancer-free women (n~1,350); (2) examine associations of stromal markers with MBD (n~1,350); and (3)
examine associations of stromal markers in women with a previous benign biopsy and the risk of subsequent
BCa in a nested case-control design (~400 cases/~975 controls). This proposal leverages established tissue
resources, use of validated multiplex immunoflourence for stromal markers, and automated image analysis for
MBD assessment. Understanding the associations of BCa risk factors with stromal markers will advance our
knowledge on its role in breast carcinogenesis in epidemiologic studies. We will generate the first
comprehensive data on the stromal markers’ expression in non-cancer breast and will identify markers that
could significantly advance future risk prediction. Stromal activity is potentially modifiable via a variety of
targeted therapies; if our project successfully demonstrates an association between stromal markers in benign
breast tissue and increased BCa risk and/or high MBD, these findings could eventually translate into
pharmaceutical interventions aimed at primary BCa prevention in high-risk women with high MBD and/or BBD.
Importantly, these findings would apply to a large segment of women undergoing routine biopsies and those
with h...

## Key facts

- **NIH application ID:** 10748124
- **Project number:** 1R01CA277817-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Rulla M Tamimi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $758,543
- **Award type:** 1
- **Project period:** 2023-07-03 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10748124

## Citation

> US National Institutes of Health, RePORTER application 10748124, Stromal contributions to breast carcinogenesis (1R01CA277817-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10748124. Licensed CC0.

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