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Locoregional indicators of systemic spread in breast cancer: insights from standard-of-care imaging and ¹⁸F-FDG PET/CT

Ann Nucl Med. 2025 Nov 12. doi: 10.1007/s12149-025-02124-6. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary role of 18F-FDG PET/CT at the initial diagnosis of breast cancer is to detect distant metastases. This study aimed to investigate locoregional characteristics associated with distant metastasis, based on clinicopathological factors, standard-of-care (SOC) imaging, and 18F-FDG PET/CT-including a novel PET parameter, subcutaneous/cutaneous uptake (SCU).

METHODS: This retrospective study included patients with newly diagnosed, unilateral invasive breast cancer who underwent pretreatment 18F-FDG PET/CT. Associations between distant metastasis and the following parameters-including age, SOC imaging-based clinical T and N stage, histology, histological grade, and subtype, as well as tumor SUVmax, subareolar SUV ratio (sSUVr), and subcutaneous/cutaneous uptake (SCU) on PET-were assessed using the Mann-Whitney U test, Fisher’s exact test, and logistic regression. Subgroup analyses were also performed after stratifying patients by locoregional clinical stage (I-IIIA vs. IIIB-C).

RESULTS: Among 197 women (mean age, 56 ± 14 years), distant metastasis was identified in 23 (11.6%). The prevalence of distant metastasis at each locoregional stage in SCU-positive versus SCU-negative patients was as follows: 0% vs. 0% for stage I; 22% vs. 1% for stage IIA; 25% vs. 14% for stage IIB; 25% vs. 13% for stage IIIA; 25% vs. 33% for stage IIIB; and 50% vs. 50% for stage IIIC, with a statistically significant difference observed at stage IIA. In the total cohort, univariate analysis showed that clinical T stage (p = .005), clinical N stage (p < .001), sSUVr (p = .002), and SCU (p < .001) were significantly associated with distant metastasis. In multivariate analysis, only clinical N stages (Odd ratio [OR], 6.5-32.6; p < .001-0.02) remained independent predictors. In the stage I-IIIA subgroup, SCU (OR, 4.86; p = .048) independently predicted distant metastasis, along with age (OR, 1.07; p = .01) and clinical N stages (OR, 8.40-30.26; p = .002-0.008). In the stage IIIB-C subgroup, none of the explanatory variables had significant associations with distant metastasis.

CONCLUSIONS: Age, clinical N stages, and SCU were associated with an elevated risk of distant metastasis in the stage I-IIIA disease. SCU may serve as a novel imaging marker of systemic disease and aid in the diagnosis of distant metastasis-particularly in patients with early-stage breast cancer, where such findings can critically influence treatment strategy.

PMID:41222829 | DOI:10.1007/s12149-025-02124-6

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