Molecular Proliferation Marker Ki-67 in Breast Cancer: The Role of Vitamin D Status, Hormone Receptor Expression, and Clinicopathological Factors—A Cross-Sectional Study

Abstract

Ki-67 is a well-established nuclear biomarker of tumor cell proliferation with key importance for the molecular classification and prognostic stratification of breast cancer. This cross-sectional study included 101 women with histopathologically confirmed invasive breast cancer treated at the St. John of Dukla Oncology Center of the Lublin Region (COZL), Poland (2018–2019). Ki-67 expression was assessed immunohistochemically on formalin-fixed, paraffin-embedded tumor tissue, and independent predictors were identified using multiple linear regression. The median Ki-67 was 20% (IQR: 15–40%). Ki-67 differed significantly between molecular subtypes (Kruskal–Wallis test H = 16.122; p = 0.001; η2 = 0.138): Luminal A tumors had the lowest Ki-67 (median 18%), whereas the Luminal B, HER2-enriched, and Triple-negative subtypes showed higher values (median 30% each). Ki-67 was significantly lower in tumors expressing the estrogen receptor (p = 0.005) and progesterone receptor (p = 0.023). Because the Luminal A/B distinction incorporates a Ki-67 threshold by definition, a multivariable model excluding molecular subtype was fitted using ER, PR, HER2, menopausal status, age, BMI category, and 25(OH)D as candidate predictors. This model identified HER2 positivity (b = 11.26; p = 0.024) and postmenopausal status (b = 17.93; p = 0.017) as independent predictors of higher Ki-67, with a borderline inverse association for age (b = −0.65; p = 0.092); the model explained 10.1% of variance (R2 = 0.101; F(3,95) = 3.574; p = 0.017), and neither ER, PR, BMI, nor 25(OH)D were retained. Serum 25(OH)D concentration showed no meaningful association with Ki-67, either unadjusted (Spearman ρ = 0.035; p = 0.730) or when forced into the retained multivariable model regardless of significance (adjusted b = −0.032; 95% CI: −0.337–0.272; p = 0.834); no association was observed between circulating 25(OH)D and Ki-67 in this cohort, although indirect biological relationships cannot be excluded.