Upregulation of Endothelin-1 May Predict Chemotherapy-Induced Cardiotoxicity in Women with Breast Cancer

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 Jun 24

PMID 35743613

Authors

Krithika Krishnarao

Katelyn A Bruno

Damian N Di Florio

Brandy H Edenfield

Emily R Whelan

Logan P Macomb

Molly M McGuire

Anneliese R Hill

Jordan C Ray

Lauren F Cornell

Winston Tan

Xochiquetzal J Geiger

Gary R Salomon

Erika J Douglass

DeLisa Fairweather

Mohamad H Yamani

Affiliations

Soon will be listed here.

Abstract

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% ( = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF ( = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.

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