Clinical subtypes and prognosis of invasive breast cancer with Paget’s disease: a SEER study

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Abstract
Paget's disease of the breast is rare but commonly associated with underlying carcinoma. Despite frequent HER2 overexpression, its clinical relevance in Paget's disease remains unclear. We evaluated the prognostic impact of ER and HER2 expression in invasive ductal carcinoma (IDC) with Paget's disease and assessed whether clinical subtypes affect survival outcomes. Using SEER 17 data, we identified patients with IDC and HER2 status available, diagnosed from 2010 onward. Two groups were analyzed: IDC with Paget's disease (ICD-O-3 code 8541/3, n = 1,000) and IDC alone (ICD-O-3 code 8500/3, n = 487,162). Compared to IDC alone, patients with Paget's disease had lower ER (60.5% vs. 82.0%) and PR (45.5% vs. 71.7%) expression, and higher HER2 overexpression (52.5% vs. 15.4%) (all P < 0.001). The ER + HER2 - subtype was less common in the Paget's group (34.9% vs. 71.6%), while ER - HER2 + was more frequent (29.2% vs. 4.8%) (P < 0.001). Among ER + HER2 - and ER + HER2 + subtypes, those with Paget's disease had worse breast cancer-specific survival (BCSS) than those with IDC alone (HR 1.519, 95% CI 1.074-2.149; HR 1.030, 95% CI 1.027-1.033, respectively). No BCSS differences were observed in ER - HER2 - and ER - HER2 + subtypes. ER + HER2 - subtype in IDC with Paget's disease is linked to worse BCSS, differing from IDC alone. These findings suggest distinct tumor biology in IDC with Paget's disease, highlighting the need for subtype-specific management strategies.

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