Importance of Retinoic Acid Derivatives in Breast Cancer: A Literature Review

Due to its specific accumulation in breast tissue and lower hazardous effects, Retinoic Acid (RA) has become increasingly popular in the treatment of Breast Cancer (BC). RA modulates the proliferative activity of BC cells and aids in the redifferentiation of cancer cells into normal breast epithelial cells. The HOXA5 regulates RA (homeobox A5) gene through Retinoic Acid Receptors (RAR) and Retinoid X Receptors (RXR) (-α, -β and -γ) and governs numerous cellular processes, including cellular metabolism and both primary and secondary programmed cell death. RA impairs oestrogen signalling in BC by activating Lysine-Specific histone Demethylase 1 (LSD1) proteins. RA downregulates the survivin protein when combined with other drugs like tamoxifen, taxol and interferon, thereby sensitising BC cells and promoting the progression of cell death. Through cadherin-mediated junction formation, RA regulates mammary gland homeostasis, causing BC cells to undergo lactogenic differentiation, which results in an epithelial phenotype. In the third phase of a mammary carcinoma prevention trial, retinoids reduce the incidence of second BC in older women by modulating the levels of Insulin-like Growth Factor (IGF-I) and Insulin-Like Growth Factor Binding Protein (IGFBP-3), which is its main binding protein, both of which have been connected to an increased risk of BC. Women taking tamoxifen with fenretinide experience a significantly lower rate of hot flashes compared to those taking tamoxifen alone. All-Trans Retinoic Acid (ATRA) reduces the hypercoagulation markers when taken alongside tamoxifen; hence, this combination is recommended for preoperative BC patients. RA derivatives combined with immunotherapy delay the recurrence of BC by increasing lymphocytes and natural killer cells. Targeting Breast Cancer Stem Cells (BCSC) is an effective strategy for BC management, with retinoids acting against BC by targeting BCSC. Thus, RA may help prevent chemotherapy resistance and reduce the recurrence of BC in multiple ways; still, further research is essential for an in-depth understanding of RA and BC.