Mammary Paget Disease is Not an Independent Prognostic Factor: A Contemporary SEER Analysis

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Abstract
Purpose: This study aimed to provide an updated evaluation of the clinicopathological characteristics and survival outcomes of mammary Paget disease by analyzing pure Paget, Paget + DCIS, and Paget + IDC subgroups within the contemporary SEER cohort, which includes consistent HER2 reporting and reflects the modern systemic therapy era. Methods: Cases diagnosed in the SEER database between 2010 and 2021 were analyzed. Clinicopathological parameters were compared across subgroups. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses and multivariable Cox regression models. Results: Paget-associated subgroups exhibited distinct biological profiles, characterized by lower hormone receptor positivity and markedly higher HER2 positivity compared with IDC. In unadjusted analyses, pure Paget and Paget + IDC groups demonstrated lower survival, whereas Paget + DCIS showed the most favorable outcomes (P < 0.001) . However, after adjustment for key prognostic determinants, including age, stage, grade, nodal status, and treatment, histological subgroup was not an independent predictor of OS or CSS. Conclusion: In the modern therapeutic era, survival differences across the Paget spectrum appear to reflect the underlying carcinoma’s biological and clinical characteristics rather than the presence of Paget disease itself. This study represents the most contemporary, comprehensively adjusted population-level analysis to date and clarifies that, when tumors are matched for stage and subtype, Paget disease does not independently worsen prognosis.

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