Abstract The UGT1A1*28/*28 genotype is linked to reduced UGT1A1 enzyme activity and increased toxicity risk. This study assesses the potential clinical and economic impact of preemptive UGT1A1*28 genotyping in SG-treated patients. We conducted a retrospective study (Aug 2024-Jul 2025) involving 15 metastatic breast cancer patients treated with SG. UGT1A1*28 genotyping (via KASP probes; €10.51/patient) was performed in those experiencing grade ≥3 toxicities (n=8). Clinical, hospitalization, and cost data were retrieved using official Andalusian Health Service pricing (May 2024), including DNA extraction and lab expenses. Three patients required hospitalization: One UGT1A1*28/*28 patient was admitted to the ICU (5 days) and internal medicine ward (6 days) due to septic shock with febrile neutropenia (grade 4) and other toxicities (total cost: €14,553.08)One UGT1A1*1/*28 patient was hospitalized for 11 days due to febrile neutropenia (grade 4) and gastrointestinal toxicity (€8,485.73)Another UGT1A1*28/*28 patient was admitted to the oncology ward for 3 days due to grade 4 neutropenia (€2,314.29) The total cost of preemptively genotyping all 15 patients would have been only €157.65. The median PFS among evaluable patients was 6.5 months. Two patients remained on treatment without progression at data cutoff. Although no formal comparison by genotype was performed due to sample size, patients with the UGT1A1*28/*28 genotype showed a trend toward shorter treatment duration due to early-onset toxicity and treatment discontinuation.According to RECIST 1.1 criteria, there were 2 partial responses (PR), 4 cases of stable disease (SD), 1 progressive disease (PD), and 1 unevaluable case due to early discontinuation caused by persistent toxicity (UGT1A1*28/*28 carrier).Regarding clinical management, all UGT1A1*28/*28 patients required dose reductions, treatment discontinuation, or G-CSF support. Two underwent progressive dose reductions (up to 70%), and one discontinued SG after two reductions due to persistent toxicity. Both UGT1A11/28 patients required dose adjustments: one with a 25% reduction and filgrastim prophylaxis, and another with a 75% dose. In contrast, neither of the UGT1A1*1/*1 patients required dose modification. This real-world series suggests that the UGT1A1*28 genotype is associated with a higher risk of severe toxicity, hospitalization, and dose modification in SG-treated patients. Although one UGT1A1*1/*1 patient also experienced severe toxicity, most serious events occurred in UGT1A1*28 carriers. Given the low cost of genotyping, implementing preemptive UGT1A1*28 testing prior to SG initiation may be a cost-effective strategy to anticipate and reduce serious adverse events. Prospective studies with larger cohorts are needed to confirm these findings. Citation Format: I. BLANCAS, M. MARTINEZ PEREZ, X. DIAZ VILLAMARIN, F. RODRIGUEZ SERRANO, R. MORON. Clinical and Economic Impact of Preemptive UGT1A1*28 Genotyping in Metastatic Breast Cancer Patients Treated with Sacituzumab Govitecan: Real-World Experience abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-17.
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