Impact of Vitamin D Levels on Progression-Free Survival and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Breast cancer remains the leading cause of cancer-related deaths among women despite advances in early detection. Neoadjuvant chemotherapy (NACT) is now standard for early-stage BC, with vitamin D (VD) emerging as a potential prognostic biomarker considering its positive pleiotropic effects. This review and meta-analysis assess the impact of baseline VD levels on outcomes in BC patients undergoing NACT. Methods: Inclusion criteria required patients to be over 18 years of age, have a pathologically confirmed BC diagnosis, and have their VD levels assessed prior to chemotherapy. Studies were included if they reported odds ratios (ORs) for response and/or hazard ratios (HRs) for PFS with 95% confidence intervals (CIs). A comprehensive literature search of PubMed/MEDLINE and Scopus/ELSEVIER (2014-2024) was conducted, and data were analyzed using fixed- and random-effects models, with Forest plots illustrating the results. Study quality and potential biases were assessed using the MINORS, NOS, and RoB2 scales, and statistical heterogeneity was evaluated with I² statistics and funnel plots. Results: Six studies were included in the analysis. All studies addressed stages II and III, with three also including stage I. The meta-analysis covered data from 722 patients regarding NACT response and 1033 patients for PFS. The results revealed a 22% reduction in the likelihood of non-response to NACT associated with adequate VD levels (low/deficient VD vs. high/sufficient VD; OR: 0.78; 95% CI: 0.30-1.25; p = 0.001) and a 35% reduction in progression risk with sufficient baseline VD levels (low/deficient VD vs. high/sufficient VD; HR: 0.65; 95% CI: 0.33-0.97; p < 0.001). Conclusions: These findings highlight the significance of maintaining adequate vitamin D levels in BC treatment and encourage further studies to unravel the role of VD on cancer biology.

Keywords: breast cancer; meta-analysis; neoadjuvant therapy; progression-free survival; response; vitamin D.

Figure 1

Flowchart of the study selection process.

Figure 2

Funnel plots illustrating the selected studies for response to NACT (A) and progression-free survival (PFS) (B). The x-axis denotes the estimated outcome (OR: odds ratio; HR: hazard ratio), while the y-axis indicates the standard error. For response to NACT (A), the heterogeneity test yielded a significant result (Q = 9.9527, DF = 3, P = 0.0190), with an I² (inconsistency) value of 69.86% (95% CI: 13.33% to 89.52%). Due to the considerable heterogeneity, a random-effects model was employed for the meta-analysis of the response to NACT. The funnel plot for PFS (B) shows no significant asymmetry, implying the absence of publication bias or small-study effects in this particular analysis [27,28,29,30,31,32].

Figure 3

Forest graphs illustrating the pooled estimates of odds ratio (OR) of response (A) and progression-free survival (PFS) (B), stratified by varying levels of vitamin D in patients with breast cancer treated with neoadjuvant chemotherapy. The graphs present the pooled estimates using fixed- and/or random-effects models. To facilitate interpretation, an arrow on the x-axis indicates the trajectory of sufficient vitamin D levels and its relationship with varying risk, relative to the unit. Weights, which depend on the sample size and precision of estimates and reflect the relative contribution of each study to the meta-analysis, are reported to the right of the graphs. CI: Confidence Interval; HR: Hazard Ratio; NACT: NeoAdjuvant ChemoTherapy [27,28,29,30,31,32].