Background. Older patients (pts) receiving chemotherapy (CT) for early-breast cancer (EBC) are at increased risk of treatment-related toxicity, yet tools to guide risk-adapted decision-making are limited. Growth Differentiation Factor 15 (GDF15) is a stress-induced cytokine associated with systemic inflammation, cachexia, and cellular senescence. We have previously demonstrated that GDF15 correlates with frailty and worse prognosis, in older EBC pts. Emerging evidence suggests that GDF15 may also predict CT-related toxicity. Methods. We included pts aged ≥70 years with operated EBC who received adjuvant CT across 3 oncogeriatric trials, and for whom a pre-treatment blood sample was collected and stored. Pts were classified as Fit, Vulnerable or Frail according to a 43-item Frailty Index (43-FI) developed by our group, and the Balducci classification (Balducci-c). Serum GDF15 levels were measured. We recorded on CT-related relevant toxicities, defined as CTCAE v 5.0 grade (G)3/G4 events or G2 occurring in more than 10% of pts, and assessed toxicity-predictive scores (CRASH, CARG, and CARG-BC). We evaluated the association among GDF15, frailty classifications (43-FI and Balducci-c), and toxicity, as well as correlations with toxicity-predictive scores. Results. We identified 56 pts treated with CT. CT-regimens included taxane (T)-based (n=36), anthracycline (A)-based (n=6), A+T-combinations (n=12), and others (n=2). Toxicity occurred in 23 pts (41%), and was more frequent for A+T-combinations (67%). The most common toxicities were fatigue (30%), anemia (26%) and diarrhea (13%). GDF15 levels were significantly higher in pts who experienced toxicity compared to those who did not (p = 0.0054). Toxicity rates increased with frailty severity in both classifications: 43-FI Fit 21% vs Vulnerable 53% (p=0.043); Balducci-c Fit 33% vs Vulnerable 67% (p=0.051). CRASH showed moderate correlation with GDF15 (R=0.37), whereas CARG and CARG-BC demonstrated weaker or inconsistent associations. Conclusions. GDF15 is a promising biomarker for identifying older breast cancer pts at higher risk of CT-related toxicity. When combined with structured frailty assessments, it may support personalized treatment strategies in geriatric oncology.
Risi, E., Picca, A., Biagioni, C., Benelli, M., Colloca, G. F., Fusco, D., Moretti, V. E., Livraghi, L., Malorni, L., Palmieri, V. E., Papa, A. F., Vannini, G., Berra, D., Del Monte, F., Calvani, R., Calvani, D., Mancini, C., Mottino, G., Marzetti, E., Biganzoli, L., (Abstract) 240eP Chemotherapy-related toxicity prediction in older patients with early breast cancer, <<ANNALS OF ONCOLOGY>>, 2025; 36 (S2): S301-S301. [doi:10.1016/j.annonc.2025.08.670] [https://hdl.handle.net/10807/326577]
240eP Chemotherapy-related toxicity prediction in older patients with early breast cancer
Colloca, Giuseppe Ferdinando;Fusco, Domenico;Moretti, Violante Elena;Papa, Antonio Fabrizio;Calvani, Riccardo;Marzetti, Emanuele;
2024
Abstract
Background. Older patients (pts) receiving chemotherapy (CT) for early-breast cancer (EBC) are at increased risk of treatment-related toxicity, yet tools to guide risk-adapted decision-making are limited. Growth Differentiation Factor 15 (GDF15) is a stress-induced cytokine associated with systemic inflammation, cachexia, and cellular senescence. We have previously demonstrated that GDF15 correlates with frailty and worse prognosis, in older EBC pts. Emerging evidence suggests that GDF15 may also predict CT-related toxicity. Methods. We included pts aged ≥70 years with operated EBC who received adjuvant CT across 3 oncogeriatric trials, and for whom a pre-treatment blood sample was collected and stored. Pts were classified as Fit, Vulnerable or Frail according to a 43-item Frailty Index (43-FI) developed by our group, and the Balducci classification (Balducci-c). Serum GDF15 levels were measured. We recorded on CT-related relevant toxicities, defined as CTCAE v 5.0 grade (G)3/G4 events or G2 occurring in more than 10% of pts, and assessed toxicity-predictive scores (CRASH, CARG, and CARG-BC). We evaluated the association among GDF15, frailty classifications (43-FI and Balducci-c), and toxicity, as well as correlations with toxicity-predictive scores. Results. We identified 56 pts treated with CT. CT-regimens included taxane (T)-based (n=36), anthracycline (A)-based (n=6), A+T-combinations (n=12), and others (n=2). Toxicity occurred in 23 pts (41%), and was more frequent for A+T-combinations (67%). The most common toxicities were fatigue (30%), anemia (26%) and diarrhea (13%). GDF15 levels were significantly higher in pts who experienced toxicity compared to those who did not (p = 0.0054). Toxicity rates increased with frailty severity in both classifications: 43-FI Fit 21% vs Vulnerable 53% (p=0.043); Balducci-c Fit 33% vs Vulnerable 67% (p=0.051). CRASH showed moderate correlation with GDF15 (R=0.37), whereas CARG and CARG-BC demonstrated weaker or inconsistent associations. Conclusions. GDF15 is a promising biomarker for identifying older breast cancer pts at higher risk of CT-related toxicity. When combined with structured frailty assessments, it may support personalized treatment strategies in geriatric oncology.
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