Vol. 7, Issue 2, Part D (2025)

Background: Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide. Conventional therapies, including chemotherapy, radiotherapy, and endocrine therapy, are effective but often limited by toxicity, resistance, and tumor heterogeneity. Phytotherapeutic compounds have emerged as complementary and alternative strategies with promising anticancer potential.

Objective: This review aims to provide an integrative analysis of the molecular and cellular mechanisms by which phytotherapeutic compounds exert chemopreventive and therapeutic effects in breast cancer, with an emphasis on modulation of oncogenic signaling pathways and the tumor microenvironment (TME).

Methods: We performed a comprehensive analysis of preclinical (in vitro and in vivo) and clinical studies, focusing on polyphenols, terpenoids, alkaloids, flavonoids, isoflavones, sulfur-containing compounds, and other bioactives. Mechanistic insights, synergy with conventional therapies, and translational challenges were synthesized.

Results: Phytochemicals such as curcumin, resveratrol, EGCG, quercetin, genistein, sulforaphane, thymoquinone, berberine, and withaferin A exhibit anti-proliferative, pro-apoptotic, cell cycle-arresting, anti-metastatic, and autophagy-modulating effects. They target key oncogenic pathways, including PI3K/Akt/mTOR, NF-κB, MAPK/ERK, Wnt/β-catenin, and estrogen receptor signaling, while influencing the TME through angiogenesis inhibition, immune modulation, and extracellular matrix remodeling. Preclinical studies demonstrate enhanced efficacy when combined with chemotherapy, radiotherapy, or endocrine therapy. Clinical data, though limited, indicate favorable safety profiles and biomarker modulation.

Conclusion: Phytotherapeutic compounds offer a multifaceted, mechanistically rational approach to breast cancer management, either as monotherapy or in combination with conventional treatments. Challenges such as bioavailability, standardization, and clinical translation remain, highlighting the need for well-designed trials and advanced delivery systems.