
Breast cancer is one of the most commonly diagnosed cancers among women worldwide and remains a leading cause of cancer-related mortality. Among its subtypes, Triple-Negative Breast Cancer (TNBC) is considered one of the most aggressive and therapeutically challenging forms because of the absence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor-2 (HER2). Due to the lack of these receptors, TNBC patients have limited treatment options and often depend on chemotherapy, surgery, and radiotherapy, which are associated with recurrence, metastasis, and poor prognosis.Recent advances in cancer biology have highlighted the importance of metabolic pathways and micronutrients in tumor progression and therapy. Vitamin K and riboflavin (vitamin B2) have emerged as promising bioactive compounds due to their ability to influence oxidative stress, mitochondrial metabolism, apoptosis, inflammation, and cancer cell signaling pathways. Vitamin K, especially vitamin K2 (menaquinone), has demonstrated anti-proliferative and pro-apoptotic activity in several cancer cell models including breast cancer. It modulates pathways such as NF-κB, PI3K/Akt, and MAPK while also affecting angiogenesis and cancer stem cell survival.Riboflavin acts as a precursor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), essential cofactors involved in mitochondrial respiration and cellular redox balance. TNBC cells exhibit altered metabolism and increased oxidative stress, making them highly dependent on flavin-mediated enzymatic reactions. Studies suggest that targeting riboflavin transporters and flavoprotein-dependent pathways can impair tumor growth and sensitize cancer cells to chemotherapy and photodynamic therapy.Emerging nanotechnology-based delivery systems, including riboflavin-functionalized nanoparticles and vitamin-mediated targeted drug delivery, further support the therapeutic potential of these micronutrients. Although current evidence is largely preclinical, early findings indicate that vitamin K and riboflavin may serve as supportive or adjunctive agents in TNBC management.This review summarizes the molecular mechanisms, pharmacological actions, preclinical evidence, therapeutic applications, and future research prospects of vitamin K and riboflavin in TNBC treatment.
