Abstract:
Background: Breast cancer remains the most commonly diagnosed malignancy and a leading cause of cancer-related mortality among women worldwide. Despite advances in diagnosis and treatment, its global burden continues to rise, highlighting the need for modifiable prognostic factors. Vitamin D, a secosteroid hormone involved in cell proliferation, apoptosis, and immune regulation, has been proposed as a potential protective and prognostic factor in breast cancer. Experimental evidence suggests anticancer effects mediated through the vitamin D receptor, including inhibition of tumor growth and angiogenesis. However, epidemiological and clinical findings remain inconsistent, necessitating a comprehensive evaluation of current evidence.
Methods: A systematic review that followed PRISMA guidelines was conducted using randomized controlled trials, cohort studies, and observational studies. Study quality and risk of bias were assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for randomized trials. No studies were excluded based solely on quality; however, limitations were considered during interpretation. Due to substantial heterogeneity in study design, vitamin D assessment, and outcomes, a meta-analysis was not feasible. Therefore, a narrative synthesis was performed. Risk of bias across studies—including selection bias, confounding, and reporting bias—was independently evaluated by multiple reviewers. Ethical approval was not required.
Results: A total of 26 studies were included. Most observational studies demonstrated that higher circulating 25-hydroxyvitamin D levels were associated with reduced breast cancer–specific mortality and improved overall survival. Patients with vitamin D deficiency consistently showed poorer outcomes, including increased disease progression and mortality. These findings align with meta-analytic evidence suggesting significantly lower mortality among patients with higher vitamin D levels . However, interventional studies on vitamin D supplementation showed mixed results, with some reporting modest survival benefits while others found no significant effect. Variability in dosing, baseline vitamin D status, and patient characteristics contributed to these inconsistencies. Additional modifying factors included body mass index, menopausal status, tumor subtype, and geographic variation.
Conclusion: Adequate vitamin D status appears to be associated with improved survival and reduced mortality in breast cancer patients, while deficiency is linked to poorer prognosis. However, the therapeutic role of vitamin D supplementation remains inconclusive. Further large-scale, well-designed randomized controlled trials are needed to clarify its clinical utility and optimize treatment strategies.
