This study examined whether prior chemotherapy (or radiotherapy, age, smoking, obesity) was associated with clonal hematopoiesis of indeterminate potential (CHIP) in 189 stage I–III breast cancer survivors, with blood drawn a median of 136.5 months (~11 years) after diagnosis, using buffy-coat whole-exome sequencing and a 100-gene hematopoietic-driver panel.
CHIP was detected in 54/189 (28.6%) survivors by panel and 67/189 (35.4%) exome-wide, with DNMT3A and TET2 as dominant genes. Prior chemotherapy was not associated with panel-defined CHIP (OR 0.77; 95% CI 0.40–1.48; p = 0.432) or exome-wide variant positivity (OR 0.89; 95% CI 0.48–1.67; p = 0.721); no clinical variable tested reached significance.
- Single time-point blood draw limits ability to track CHIP emergence or clonal dynamics longitudinally. - The cohort is limited to female breast cancer survivors, restricting generalizability to other cancers or sexes. - Relatively modest sample size (n=189) may limit power to detect smaller subgroup effects (e.g., by chemotherapy regimen type).
Long-term breast cancer survivors do not appear to have a higher burden of CHIP attributable to prior chemotherapy at roughly 11 years post-diagnosis. Clinicians using blood-based genomics in this population should be aware that CHIP is common (~29–35%) but likely reflects background aging rather than treatment-related clonal selection.
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