Serum prolactin as a shared inflammation-associated signal across inflammatory breast conditions: a four-group comparative study with exploratory inflammatory breast cancer subtype analysis.
- 1Department of Breast Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- 2Department of Breast Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract
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. A single-center, retrospective, four-group comparison [healthy controls (HC): n=121; invasive ductal carcinoma (IDC): n=123; IBC: n=42; NPM: n=226; total: N=512] was conducted on consecutive patients evaluated between January 2022 and December 2025. Three prespecified contrasts (NPM vs. HC, IBC vs. IDC, and IBC vs. 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. PRL was elevated in both inflammatory conditions [NPM vs. HC: adjusted odds ratio (OR) 3.88, 95% confidence interval (CI): 2.52-6.20; P<0.001; IBC vs. IDC: adjusted OR 4.03, 95% CI: 2.19-7.97, median PRL 342 vs. 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. 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.
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BibTeX
@article{chen2026serum,
title = {{Serum prolactin as a shared inflammation-associated signal across inflammatory breast conditions: a four-group comparative study with exploratory inflammatory breast cancer subtype analysis.}},
author = {Weili Chen and Mengting Li and Mengting Dong and Xinyue Zhang and Lingdi Qin and Xiaohong Xue and Ke Jiang and Hua Wan},
journal = {Gland surgery},
year = {2026},
month = oct,
doi = {10.21037/gs-2026-0582},
url = {https://europepmc.org/article/MED/42996861},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Serum prolactin as a shared inflammation-associated signal across inflammatory breast conditions: a four-group comparative study with exploratory inflammatory breast cancer subtype analysis.
AU - Weili Chen
AU - Mengting Li
AU - Mengting Dong
AU - Xinyue Zhang
AU - Lingdi Qin
AU - Xiaohong Xue
AU - Ke Jiang
AU - Hua Wan
PY - 2026
DA - 2026/10/26
JO - Gland surgery
DO - 10.21037/gs-2026-0582
UR - https://europepmc.org/article/MED/42996861
AB - 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. A single-center, retrospective, four-group comparison [healthy controls (HC): n=121; invasive ductal carcinoma (IDC): n=123; IBC: n=42; NPM: n=226; total: N=512] was conducted on consecutive patients evaluated between January 2022 and December 2025. Three prespecified contrasts (NPM vs. HC, IBC vs. IDC, and IBC vs. 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. PRL was elevated in both inflammatory conditions [NPM vs. HC: adjusted odds ratio (OR) 3.88, 95% confidence interval (CI): 2.52-6.20; P<0.001; IBC vs. IDC: adjusted OR 4.03, 95% CI: 2.19-7.97, median PRL 342 vs. 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. 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.
SN - 2227-684X
SN - 2227-8575
ER -