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Incidence and Outcomes of Atrial Arrhythmia with CDK4/6 Inhibitors in HR-Positive / HER2-Negative Breast Cancer

Nathaniel E Davis1, Joerg Herrmann2, David O Hodge3

  • 1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Medrxiv : the Preprint Server for Health Sciences
|August 13, 2025
PubMed
Abstract

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors pose a low risk of atrial arrhythmias (AA) in breast cancer patients. This condition is linked to increased mortality, underscoring the need for monitoring.

Area of Science:

  • Oncology
  • Cardiology
  • Pharmacology

Background:

  • Hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer treatment increasingly involves cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
  • Emerging evidence suggests potential cardiotoxicity, specifically atrial arrhythmias (AA), associated with CDK4/6 inhibitor use.
  • Understanding the incidence and outcomes of AA is crucial given the expanding indications for these therapies.

Purpose of the Study:

  • To determine the incidence of new-onset AA in patients with HR+/HER2- breast cancer treated with CDK4/6 inhibitors.
  • To evaluate associated outcomes, including cerebrovascular events and all-cause mortality.
  • To compare AA incidence across different CDK4/6 inhibitor agents.

Main Methods:

  • Retrospective cohort study of 2,782 patients treated with CDK4/6 inhibitors for HR+/HER2- breast cancer (2015-2024).
  • Primary outcome: incidence of new-onset AA (atrial fibrillation, flutter, or tachycardia).
  • Secondary outcomes: cerebrovascular events and all-cause mortality. Kaplan-Meier and Cox regression analyses were employed.

Main Results:

  • New-onset AA occurred in 45 patients, with a cumulative 5-year incidence of 2.8%.
  • No significant difference in AA incidence was found between palbociclib, abemaciclib, and ribociclib (p=0.44).
  • Age at treatment was the sole independent predictor of AA (HR 1.073, p<0.001). New-onset AA correlated with increased mortality (HR 1.56, p=0.012).

Conclusions:

  • CDK4/6 inhibitor therapy is associated with a low but clinically significant risk of new-onset AA.
  • New-onset AA following CDK4/6 inhibitor use is linked to increased mortality.
  • No significant difference in AA risk exists between individual CDK4/6 inhibitor agents; prospective studies are warranted.

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