# Cardiovascular Impact of Near-complete Estrogen Deprivation for Breast Cancer

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $621,859

## Abstract

Abrupt menopause induction together with anti-estrogen therapy improves recurrence-free
survival in breast cancer and is a new standard of care for premenopausal women with hormone
receptor (HR)-positive breast cancer. This near-complete estrogen deprivation (NCED) therapy
also places these women at risk of organ compromise associated with early hypoestrogenemia.
Early hypoestrogenemia in women with non-cancerous reasons for premature menopause is
associated with significant cardiovascular (CV) compromise including atherosclerosis and
coronary artery disease, which can be detected preclinically by myocardial perfusion imaging and
computed tomography angiography. Less is known about how NCED therapy will impact CV
health in the tens of thousands of premenopausal women diagnosed with HR-positive breast
cancer each year who will see NCED therapy. It is critical to understand the early natural history
of this risk because clinical CV disease related to hypoestrogenemia will not be reversible. Given
the prevalence of HR-positive breast cancer and marked improvements in survival following
breast cancer, long-term CV sequalae from cancer treatments have the potential to both impact
large numbers of women and offset these survival gains. We will study the early impact of NCED
on the CV system to identify pre-clinical markers of myocardial compromise. The CV health of
women initiating NCED will be assessed by comprehensive, quantitative serial cardiac magnetic
resonance imaging stress studies over a two-year period to document changes in flow of both
small and large CV vessels as well as overall left ventricular structure and function.
We will test the overarching hypothesis that premenopausal women receiving NCED for HR-
positive breast cancer have CV declines that can be identified preclinically using the following
aims: Characterize and quantify the extent of microvascular injury and perfusion changes
experienced during early NCED therapy; Characterize and quantify the extent structural and
functional alterations to the aorta and left ventricle while on NCED therapy; Identify potential
biomarkers and additional risk factors for CV decline in patients receiving NCED. The knowledge
derived from these aims will provide an understanding of which patients are at risk of CV
compromise from NCED. These studies will further enable development of standard of care
predictive tools to assess CV decline in women on NCED before it is clinically apparent with the
goal of allowing women to safely remain on anti-neoplastic regimens and thereby lower both the
burdens of cancer and cardiovascular treatment-related toxicity.

## Key facts

- **NIH application ID:** 10444580
- **Project number:** 1R01HL159393-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jennifer Hawthorne Jordan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $621,859
- **Award type:** 1
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444580

## Citation

> US National Institutes of Health, RePORTER application 10444580, Cardiovascular Impact of Near-complete Estrogen Deprivation for Breast Cancer (1R01HL159393-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10444580. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*