Serum prolactin as a shared inflammation-associated signal across inflammatory breast conditions: a four-group comparative study with exploratory inflammatory breast cancer subtype analysis
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Inflammatory breast cancer (IBC) and nonpuerperal mastitis (NPM) present with closely overlapping inflammatory breast signs yet require entirely different management. No previous study has reported on the serum prolactin (PRL) level in the context of IBC or compared the PRL level between IBC and NPM. This study aimed to characterize serum PRL in IBC relative to NPM, invasive ductal carcinoma, and healthy controls, and to determine whether PRL adds discriminative information beyond systemic inflammatory markers for distinguishing IBC from NPM. Methods: NPM) were analyzed via multivariable logistic regression adjusted for age, body mass index (BMI), and menopausal status. Within-group PRL-inflammation correlations were compared across groups via Fisher r-to-z transformation. A combined model consisting of log(PRL), log[C-reactive protein (CRP)], log(neutrophil-to-lymphocyte ratio) and age, was evaluated for IBC-NPM discrimination. Results: 208 mIU/L, P<0.001]-the first report of PRL elevation in patients with IBC. However, PRL could not discriminate IBC from NPM (adjusted OR 0.94; 95% CI: 0.31-2.97; P=0.91). A four-variable model discriminated IBC from NPM (apparent area under the curve [AUC] 0.895; optimism-corrected 0.879), but this was driven by CRP (OR 0.68, P=0.04) and age (OR 1.19, P<0.001), not PRL (P=0.62). In NPM, PRL correlated with interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α (P<0.001; false-discovery rate [FDR] q<0.001); this coupling was not detectable in the IBC cytokine subset (n=31; Fisher r-to-z for IL-6: P=0.10). Within IBC, hyperprolactinemia (PRL >496 mIU/L; 13/42, 31%) appeared more frequent in luminal B human epidermal growth factor receptor 2 (HER2)+ and triple-negative breast cancer (TNBC) (Monte Carlo P=0.03; post hoc Fisher OR 10.4, P=0.006), with no cases in luminal A (0/8) or HER2-enriched (0/4). However, with only 42 IBC patients and 13 hyperprolactinemic cases, statistical power is severely limited, and this finding is hypothesis-generating only. Conclusions: Serum PRL is elevated across inflammatory breast conditions and appears to behave as a shared, inflammation-associated endocrine marker rather than a marker that distinguishes IBC from NPM. Serum PRL is elevated across inflammatory breast conditions and behaves as a shared inflammation-associated marker rather than a discriminator between IBC and NPM. Separation between the two conditions was driven by CRP and age. Within IBC, hyperprolactinemia appeared more frequent in aggressive subtypes, but this is strictly an exploratory, hypothesis-generating observation requiring prospective validation in an independent, adequately powered cohort. Because tumor prolactin receptor (PRLR) expression was not measured, any inference regarding PRL/PRLR pathway activation in IBC remains indirect.
Source: Gland Surgery
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223863175