Association of tissue Vitamin D Receptor expression with Breast Cancer Molecular Subtypes in Kenyan Women
Date of Award
Master of Medicine (MMed)
Dr. Shahin Sayed
Dr. Geoffrey Omuse
Prof. Ronald Wasike
Pathology (East Africa)
Background: Previous studies have shown that reduced vitamin D receptor expression in breast cancer tissue is associated with worse disease outcomes. Furthermore, studies show that estrogen negative and triple negative breast cancer is associated with a poor prognosis and a low breast tissue vitamin D receptor (VDR) expression. Other studies also report that low serum vitamin D levels are associated with more aggressive breast cancer.
Methods: This was a cross-sectional study with both a retrospective and a prospective arm. The retrospective part was nested within a larger study; previously constructed tissue microarray blocks (TMA) blocks were used for analysis of VDR expression. The prospective arm recruited women who underwent a breast biopsy for suspicious breast lesions in whom blood samples for serum vitamin D levels and tumour VDR immunohistochemistry were collected. Questionnaire data on pre-determined patient and tumour characteristics were extracted from the charts. Tissue expression of VDR was analysed on immunohistochemistry and serum vitamin D levels assayed.
Results: A total of 214 cases were recruited retrospectively and 24 prospectively. There was a statistically significant difference in the VDR score of the Triple negative breast cancer (TNBC) subtype compared to the other subtypes (p value = 0.047, test = ANOVA: Kruskal Wallis Test). There was a positive correlation of VDR score and tumour size. There was a weak negative correlation between VDR score and human epidermal growth factor receptor 2 (HER 2) but no correlation with ER and PR. There was a positive correlation between serum vitamin D levels and VDR Immunoreactive score (IRS).
Conclusions: Our results suggest that low or negative VDR score is a marker of poor prognosis in breast cancer as the expression was low in TNBC. However, high VDR score was not associated with ER or PR expressing tumours. The weak negative correlation with tumour size suggests an association of low VDR expression with aggressive tumour features. A randomized controlled trial exploring the utility of vitamin D supplementation or other VDR ligand analogues in TNBC is recommended. A larger study is recommended to determine if indeed there is a correlation between serum vitamin D levels and VDR expression.
Kimondo, M. (2018). Association of tissue Vitamin D Receptor expression with Breast Cancer Molecular Subtypes in Kenyan Women (Unpublished master's dissertation). Aga Khan University, East Africa.