Plant natural modulators in breast cancer prevention: status quo and future perspectives reinforced by predictive, preventive, and personalized medical approach.

In contrast to the genetic component in mammary carcinogenesis, epigenetic alterations are particularly important for the development of sporadic breast cancer (BC) comprising over 90% of all BC cases worldwide. Most of the DNA methylation processes are physiological and essential for human cellular and tissue homeostasis, playing an important role in a number of key mechanisms. However, if dysregulated, DNA methylation contributes to pathological processes such as cancer development and progression. A global hypomethylation of oncogenes and hypermethylation of tumor-suppressor genes are characteristic of most cancer types. Moreover, histone chemical modifications and non-coding RNA-associated multi-gene controls are considered as the key epigenetic mechanisms governing the cellular homeostasis and differentiation states. A number of studies demonstrate dietary plant products as actively affecting the development and progression of cancer. "Nutri-epigenetics" focuses on the influence of dietary agents on epigenetic mechanisms. This approach has gained considerable attention; since in contrast to genetic alterations, epigenetic modifications are reversible affect early carcinogenesis. Currently, there is an evident lack of papers dedicated to the phytochemicals/plant extracts as complex epigenetic modulators, specifically in BC. Our paper highlights the role of plant natural compounds in targeting epigenetic alterations associated with BC development, progression, as well as its potential chemoprevention in the context of preventive medicine. Comprehensive measures are stated with a great potential to advance the overall BC management in favor of predictive, preventive, and personalized medical services and can be considered as "proof-of principle" model, for their potential application to other multifactorial diseases.