Oral mucositis as a predictor of differential long-term adverse events and mortality in breast cancer patients treated with monoclonal antibody-drug conjugates: Evidence from a propensity score-matched cohort comparison using real-world data from 88 U.S Healthcare organizations.

e12752 Background: Monoclonal antibody-drug conjugates (mADCs) are a cornerstone of advanced breast cancer treatment, but oral mucositis as an adverse effect may contribute to long-term systemic complications and mortality, even after balancing for confounders. Methods: We conducted a retrospective cohort study using the TriNetX federated network, accessing electronic medical records from 88 healthcare organizations. Adults with breast cancer treated with mADCs were identified. Before matching, 61,279 patients without mucositis and 1,766 patients with mucositis were included. Propensity score matching balanced cohorts on age, sex, race, ethnicity, and comorbidities, yielding 1,766 matched patients per cohort. Outcomes were assessed from one day after the index event ( breast cancer diagnosis for non mucositis patients; breast cancer diagnosis plus mADC therapy with mucositis for mucositis patients) excluding > 20-year-old events. Post propensity score matching (PSM) risks of volume depletion, fluid and electrolyte disorders, respiratory infection, circulatory diseases, malaise/fatigue, pain, dysphagia, and mortality were assessed using measures of association, Kaplan-Meier survival, and event frequency. Results: After PSM, mucositis patients (Cohort 2) had higher risks for most outcomes. Volume depletion: risk 0.210 vs 0.170; P < 0.001, Hazard ratio(HR) 0.702 (95% CI, 0.612-0.805; P < 0.001, fluid/electrolyte disorders: 0.375 vs 0.300; P < 0.001; HR 0.680, respiratory infections: 0.460 vs 0.370; P < 0.001; HR 0.650, circulatory diseases: 0.610 vs 0.470; P < 0.001; HR 0.560, malaise/fatigue: 0.290 vs 0.250; P = 0.005; HR 0.780, pain: 0.150 vs 0.100 ; P < 0.001; HR 0.560, dysphagia: 0.100 vs 0.070; P = 0.002; HR 0.670, mortality: 0.250 vs 0.210; P < 0.001; HR 0.710. Mean instances showed no differences (e.g., 3.5 vs 3.2 for volume depletion; P = 0.45). Associations attenuated slightly post-PSM but remained significant. Conclusions: Even after PSM, oral mucositis in mADC-treated breast cancer patients is linked to increased long-term risks, underscoring the importance of preventive strategies to enhance patient outcomes.