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Background: Breast cancer is the most frequently diagnosed type of cancer in women, accounting for 2.1 million cases, and stands as the fifth leading cause of death. Several treatment strategies are available, such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy; however, these are associated with severe adverse effects in the patients. Objective: This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer, published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanisms of action and molecular characteristics of these compounds. Methods: The data of this review were collected from different scientific databases, such as Pub-Med, Science Direct, Google Scholarship, SciFinder, and Egyptian Knowledge Bank (EKB). Results: During the period 2016-2021, in the in vitro studies, investigation on 52 compounds of polyphenolic nature with promising anti-breast cancer activity has been conducted, while 14 com-pounds have been reported via in vivo studies. Besides, about 15 compounds have been registered as patent drugs. Different mechanisms of action and molecular targets have been reported, provid-ing a clarified basis and precise reflection of the anticancer properties of these compounds against breast cancer. Conclusion: Polyphenolics represent a comprehensive source of anticancer lead compounds against the progression of breast cancer invasion and metastasis.