In a cohort study reported in JAMA Oncology, Park et al found that clonal hematopoiesis of indeterminate potential (CHIP) was associated with an increased risk of trastuzumab-related cardiotoxicity in patients with breast cancer.
Study Details
The analysis involved data from the UK Biobank nationwide population-based cohort (patients enrolled between 2006 and 2010) and the Seoul National University Hospital (SNUH) tertiary referral center (patients enrolled between January 2004 and March 2024). Incident heart failure (HF) in the UK Biobank cohort and trastuzumab-related cardiotoxic effects in the SNUH cohort were the main outcome measures.
Key Findings
A total of 15,729 patients with breast cancer from the UK Biobank cohort and 454 patients with breast cancer who received trastuzumab from the SNUH cohort were included in the analyses.
In the UK Biobank cohort, trastuzumab exposure was associated with increased risk of incident HF; the highest risk was observed among CHIP-positive patients with trastuzumab exposure vs CHIP-negative patients with no trastuzumab exposure (adjusted subdistribution hazard ratio [HR] = 4.57, 95% confidence interval [CI] = 1.85–11.29, P < .001).
In the SNUH cohort, for patients with vs without CHIP, the 2-year cumulative incidence values for trastuzumab-related cardiotoxic effects were 15.7% vs 5.0% on European Society of Cardiology (ESC) criteria (P = .001), 19.9% vs 10.8% on Canadian Trastuzumab Working Group criteria (P = .01), and 20.9% vs 11.3% on Cardiac Review and Evaluation Committee criteria (P = .02). Using ESC criteria, CHIP positivity (variant allele frequency ≥ 1.0%) was associated with an increased risk of cardiotoxic effects in multivariable competing risk analysis (adjusted subdistribution HR = 1.91, 95% CI = 1.32–2.76).
The investigators concluded: “In this cohort study, the presence of CHIP was associated with increased susceptibility to trastuzumab-related cardiotoxic effects.”
Jun-Bean Park, MD, PhD, and Youngil Koh, MD, PhD, of Seoul National University Hospital and Seoul National University College, Seoul, Republic of Korea, are the corresponding authors for the JAMA Oncology article.
DISCLOSURE: The study was funded by the National Research Foundation of Korea and others. For full disclosures of the study authors, visit jamanetwork.com.
