Serum 25-Hydroxyvitamin D Levels in Breast Cancer Patients: A Cross-Sectional Analysis by Molecular Tumor Subtypes

Background: Vitamin D deficiency has been implicated in breast cancer pathogenesis and prognosis. However, the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and molecular breast cancer subtypes remains incompletely understood. Methods: This cross-sectional study included 168 women (89 breast cancer patients, 79 healthy controls) from Poland. Serum 25(OH)D was measured by electrochemiluminescence immunoassay. Blood samples were collected year-round, with 54% obtained during winter/spring months (October-March). Molecular subtypes (luminal A, luminal B, HER2-enriched, triple-negative) were classified by immunohistochemistry. Results: Mean 25(OH)D was 30 ± 13 ng/mL, with 55% showing insufficiency (<30 ng/mL). No significant differences were observed between patients and controls (p = 0.93). A borderline non-significant trend was observed across molecular subtypes (p = 0.055). HER2-enriched tumors showed descriptively higher concentrations (37.6 ng/mL, 95% CI: 29.5-45.8) compared to luminal A (31.0 ng/mL), luminal B (26.4 ng/mL), and triple-negative (25.9 ng/mL). A significant subtype × season interaction was detected (p = 0.015), though interpretation is limited by the absence of a main seasonal effect (p = 0.64). Age (OR = 1.06, p = 0.023) and BMI (OR = 1.06, p = 0.090) predicted vitamin D deficiency. Conclusions: Vitamin D insufficiency is prevalent in breast cancer patients and healthy women. In this exploratory analysis with limited statistical power, no definitive associations between 25(OH)D and molecular subtype were established. The descriptive trend suggesting higher vitamin D in HER2-enriched tumors requires validation. Limitations: Small sample sizes (n = 11-35 per subtype) and post-surgical blood collection limit interpretation; findings require validation in larger cohorts.