Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms

Aldo Giudice, Antonio Barbieri, Sabrina Bimonte, Marco Cascella, Arturo Cuomo, Anna Crispo, Giovanni D'arena, Massimiliano Galdiero, Maria Elena Della Pepa, Gerardo Botti, Michele Caraglia, Mario Capunzo, Claudio Arra, Maurizio Montella

Research output: Contribution to journalReview articlepeer-review


Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

Original languageEnglish
Pages (from-to)4937-4953
Number of pages17
JournalOncoTargets and Therapy
Publication statusPublished - Jan 1 2019


  • Breast carcinogenesis
  • Depurinating estrogen-DNA adducts
  • Dietary phytochemicals
  • Nuclear factor erythroid 2-related factor 2
  • Reactive estrogen quinones

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)


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