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

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

Research output: Contribution to journalArticlepeer-review


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% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 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 (p = 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.

Original languageEnglish (US)
Article number3547
JournalJournal of Clinical Medicine
Issue number12
StatePublished - Jun 1 2022


  • angiotensin II type I receptor
  • biomarkers
  • chemotherapy-induced cardiotoxicity
  • endothelin 1

ASJC Scopus subject areas

  • Medicine(all)


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