Clonal Hematopoiesis and Risk of Trastuzumab-Related Cardiotoxic Effects

Area of Science:

• Cardiology
• Oncology
• Genetics

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased cardiovascular and malignant disease risks.
• Trastuzumab is a vital therapy for breast cancer but carries risks of cardiotoxicity.

Purpose of the Study:

• To investigate the association between CHIP and trastuzumab-induced cardiotoxicity in breast cancer patients.
• To determine if CHIP presence influences the incidence of heart failure and other cardiotoxic effects.

Main Methods:

• Analysis of two cohorts: UK Biobank (population-based) and Seoul National University Hospital (tertiary referral).
• Utilized Fine-Gray competing risk models and multivariable analyses, adjusting for relevant clinical factors.
• Assessed changes in left ventricular ejection fraction (LVEF) in Tet2-deficient mice following trastuzumab exposure.

Main Results:

• CHIP presence was significantly associated with increased trastuzumab-related cardiotoxic effects (adjusted subdistribution hazard ratio, 1.91; 95% CI, 1.32-2.76) using ESC criteria.
• Trastuzumab treatment led to significant LVEF reduction in Tet2-deficient mice, but not in other experimental groups.
• Higher incidence of cardiotoxic effects observed in CHIP-positive patients across different clinical criteria.

Conclusions:

• The presence of CHIP is linked to a heightened susceptibility to cardiotoxic effects from trastuzumab therapy.
• Findings suggest CHIP may be a predictive biomarker for cardiotoxicity in breast cancer patients receiving trastuzumab.
• Further research is warranted to explore mechanisms and clinical management strategies.