Key result
Each doubling of early-peak GDF-15 ratio is linked to ~1.5% decline in LVEF.
Why the study?
GDF-15 is induced by mechanisms central to anthracycline cardiotoxicity, but whether early changes in GDF-15 after breast cancer therapy relate to subsequent cardiac dysfunction was not established.
Do early increases and longitudinal trajectories in GDF-15 correlate with subsequent declines in cardiac function and structure in women receiving anthracycline and/or trastuzumab breast cancer therapy?
Cohort (n=366)
Do early increases and longitudinal trajectories in GDF-15 correlate with subsequent declines in cardiac function and structure in women receiving anthracycline and/or trastuzumab breast cancer therapy?
Early increases in GDF-15 during anthracycline and/or trastuzumab breast cancer therapy are associated with modest subsequent declines in left ventricular ejection fraction and longitudinal strain, supporting its potential role as a biomarker of subclinical cardiotoxicity.
Answers are grounded in this paper and cite their sources.
Early GDF-15 rises may flag systolic dysfunction risk during breast cancer therapy; leaves open utility for risk stratification or clinical decision-making.
BACKGROUND: Growth differentiation factor (GDF)-15 is a stress-responsive cytokine induced by mitochondrial dysfunction and genotoxic stress, mechanisms central to anthracycline cardiotoxicity. Whether early changes in GDF-15 following cancer therapy relate to subsequent cardiac dysfunction is not established. OBJECTIVES: We evaluated the longitudinal trajectory of GDF-15 and its associations with changes in cardiac function and structure following cardiotoxic cancer therapy in women with breast cancer. METHODS: In 366 women receiving anthracyclines and/or trastuzumab from the Penn Cardiotoxicity of Cancer Therapy prospective cohort study, associations between baseline, early-peak (maximum 0-6-month change), and longitudinal GDF-15 concentrations with quantitative echocardiographic measures of systolic, diastolic, and structural function over 36 months were evaluated using multivariable linear mixed-effects models. RESULTS: GDF-15 rose from a median baseline of 662 to an early-peak of 1,412 pg/mL, with trajectories differing across regimens (P = 0.004). Each doubling of the early-peak-to-baseline GDF-15 ratio was associated with a subsequent 1.5 percentage point decline in left ventricular ejection fraction (β -1.5%; 95% CI: -2.5 to -0.6; P = 0.002) and a 0.9-unit worsening in longitudinal strain (β 0.9; 95% CI: 0.4-1.4; P = 0.001). GDF-15 was not associated with diastolic outcomes, incident diastolic dysfunction, or incident cancer therapy-related cardiac dysfunction. CONCLUSIONS: In women receiving anthracycline- and/or trastuzumab-based breast cancer therapy, early increases in GDF-15 were associated with modest declines in left ventricular ejection fraction and worsening of longitudinal strain, without associations with diastolic measures. These findings support mechanistic investigation of GDF-15 in anthracycline-related cardiotoxicity. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341).
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Wilcox et al. (2026) conducted a cohort in Breast cancer treated with anthracyclines and/or trastuzumab (n=366). Early-peak-to-baseline GDF-15 ratio (each doubling) vs. Lower GDF-15 concentrations / baseline levels was evaluated on Change in left ventricular ejection fraction (LVEF) and longitudinal strain over 36 months (β -1.5%, 95% CI -2.5 to -0.6, p=0.002). Each doubling of the early-peak-to-baseline GDF-15 ratio was associated with a 1.5% decline in LVEF (95% CI -2.5 to -0.6; P=0.002) and 0.9-unit worsening in longitudinal strain (P=0.001).
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