HGF expression and its association with recurrence and poorer survival in breast cancer

Hepatocyte Growth Factor (HGF) is a multifunctional cytokine that triggers proliferation, invasion, and metastasis in tumor cells. Elevated HGF expression has been linked to poor prognosis and treatment resistance in multiple cancers, including breast cancer, where it has been implicated in tumor aggressiveness and therapy failure. We retrospectively analyzed cytoplasmic HGF expression by immunohistochemistry (Allred-based scoring) in 92 non-metastatic breast cancer patients treated between 2010 and 2024 at a single tertiary center, using a case-control design with outcome-dependent sampling: all patients with recurrence or metastasis were included, together with a random sample of disease-free patients. Clinicopathological associations, recurrence patterns, and metastatic sites were assessed with odds ratios; Kaplan–Meier curves with log-rank comparisons were used descriptively. High HGF expression was significantly associated with advanced nodal stage, locoregional recurrence, and organ-specific metastasis. High-expression patients had approximately 10-fold higher odds of recurrence (OR 10.04, 95% CI 1.25–80.61, p = 0.03), with the wide interval reflecting the small number of events. In the adjuvant radiotherapy subgroup ( n = 83), high-expression patients had approximately 8-fold higher odds of recurrence, although this did not reach statistical significance (OR 8.00, 95% CI 0.97–65.82, p = 0.053). HGF overexpression was also associated with liver ( p = 0.015), lung ( p = 0.047), and brain ( p = 0.006) metastases. Overall survival within the analyzed sample was shorter in the high-expression group (log-rank p = 0.012); owing to the sampling design, this comparison was descriptive. High HGF expression was associated with locoregional recurrence and organ-specific metastasis, suggesting a link with aggressive tumor behavior. Owing to the outcome-dependent sampling design, these findings are exploratory and do not establish prognostic value. They warrant validation in larger, prospective cohorts.