Abstract
Objective: To assess long-term systemic complications and mortality risk associated with oral mucositis (OM) in breast cancer patients treated with monoclonal antibody-drug conjugates (mADCs). Materials and Methods: Retrospective cohort study using TriNetX federated data from 88 healthcare organizations. Adult breast cancer patients receiving mADCs with (n=1,784) or without (n=61,616) OM (ICD-10 K12.31) were 1:1 propensity score-matched on race, morbidity-related factors, ECOG status, and BMI (1,784 per cohort). Outcomes, volume depletion, fluid/electrolyte disorders, respiratory and circulatory disease, malaise/fatigue, pain, dysphagia, and mortality were assessed from 1-day post-index using risk differences, Kaplan-Meier estimates, and Cox hazard ratios. Results: Mucositis patients had significantly higher risks of fluid/electrolyte disorders (39.1% vs 32.1%; HR 0.753), respiratory disease (48.5% vs 39.0%; HR 0.697), circulatory disease (63.7% vs 51.2%; HR 0.667), pain (16.1% vs 11.7%; HR 0.664), dysphagia (10.4% vs 8.2%; HR 0.702), and mortality (26.1% vs 19.3%; HR 0.670; all P< 0.001). Volume depletion and malaise/fatigue showed attenuated absolute risk differences but persistent survival differences (HR 0.824 and 0.855). Recurrent event counts did not differ. Conclusions: OM in mADC-treated breast cancer patients predicts greater long-term systemic morbidity and mortality, despite confounder balancing. Clinical Relevance: OM may serve as a sentinel marker, identifying patients at elevated risk of systemic decline and warranting closer post-therapy surveillance rather than treatment as an isolated, self-limited toxicity. These findings support incorporating oral health assessment into oncologic risk stratification and encourage interdisciplinary oncology-dentistry collaboration for early mucositis prevention and management, which may help reduce downstream systemic morbidity and improve survival.