JMIR Publications

Background:

Human epidermal growth factor receptor-2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) are absent in TNBC, an aggressive subtype of breast cancer with few specific treatment choices and a poor prognosis. Immune regulation, cell proliferation, differentiation, and death all depend on vitamin D signaling, which is mediated by the vitamin D receptor (VDR). Although positive outcomes in breast cancer have been linked to VDR protein expression, the prognostic significance of tumor-specific VDR mRNA expression, especially in TNBC, has not been well investigated.

Objective:

This study's main goal is to assess VDR mRNA expression as a predictive biomarker in patients with triple-positive breast cancer (TPBC) versus TNBC. Examining the relationship between VDR mRNA expression and serum levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), total and ionized calcium, VDR genotypes, and the prognostic significance of VDR mRNA expression in TNBC, as determined by its correlation with clinicopathological parameters such as tumor stage, tumor grade, lymph node involvement, tumor size, treatment status, and survival endpoints like overall survival (OS) and disease-free survival (DFS). TPBC was chosen as the comparator group because it is a physiologically unique, hormone receptor-positive breast cancer subtype with a favorable prognosis, it. This allows for the study of VDR mRNA expression and vitamin D status independent of ER, PR, and HER2 signalling, which is not present in TNBC.

Methods:

In this cross-sectional, molecular, and clinical investigation, 60 female patients with breast cancer (30 TNBC and 30 TPBC) from Acharya Vinoba Bhave Rural Hospital and Siddhartha Gupta Memorial Cancer Hospital in Wardha, India, were enrolled. Using quantitative real-time PCR (qRT-PCR), tumor tissue samples will be examined for VDR mRNA expression. VDR genotyping and the measurement of serum 25(OH)D, iPTH, and calcium levels will be done using fasting blood samples. External validation will be conducted using transcriptome datasets that are accessible to the public. t-tests, ANOVA, correlation analyses, and multivariate Cox proportional hazards models will be used to evaluate relationships between VDR mRNA expression and clinicopathological factors. SPSS will be used for statistical analysis, with a significance threshold of p<0.05 and a 95% confidence range.

Results:

The project was approved by ethics in October 2024 and got intramural funding in 2024. It is anticipated that the recruiting of participants will be finished by the middle of 2026. Final results are expected to be released in early 2027, with laboratory analyses and data integration expected to be completed by late 2026.

Conclusions:

This methodology outlines a thorough, integrative method for assessing VDR mRNA expression as a possible TNBC prognostic marker. The study is anticipated to provide new insights into vitamin D–VDR signaling in TNBC and to guide future biomarker-driven research and therapeutic approaches, especially in settings with limited resources, by integrating molecular, biochemical, genetic, and clinical data.

ClinicalTrial:

The study is registered in clinical trial registry India (CTRI) portal (Ref No: Trial REF/2024/10/093899)