**8. Prevention and treatment of breast cancer with natural products: Past successes and promising future treatments**

Currently, hormones and cytotoxic drugs remain the standard treatment for metastatic breast cancers. Development of a therapeutic approach for treating tumors, tumor reoccurrence and metastatic tumors is crucial for reducing mortality in cancer patients [6]. There is an urgent need to explore agents that will be effective in preventing and treating metastasis of breast cancer. For centuries, nature has provided us with a rich source of compounds for various disease treatments. Such naturally-derived molecules have been utilized in formal drug discovery platforms of the pharmaceutical industry. Greater than 60% of new chemical entries at the National Cancer Institute from 1981-2002 were either natural products or were derived from natural products [320]. Such naturally-occurring sources can be defined by their origin and include biotic (i.e.: forests, plants, animals, birds and marine organisms) and abiotic (i.e.: land, water, air and minerals such as gold, iron, copper, and silver) components [321]. Within these categories, plants have proven to be a rich source of lead compounds (i.e: alkaloids, morphine, cocaine) or the basis for synthetic drugs (i.e: anesthetics from cocaine) [320, 321]. The complexity and variation of plant structures indicates that their evolution has naturally completed the screening process and that the creation of potent compounds makes them more likely to survive. Plants offer the advantage of abundance, and even with such clinical successes as paclitaxel (Taxol) from the yew tree, and the antimalarial agent artemisinin from *Artemisia annua*, the vast majority have not been studied [320]. Due to promising bioactivity and diversity, the plant environment offers a potential source of natural products. A vast number of studies in the discipline of epidemiology have confirmed an association between fruit and vegetable consumption and the reduced risk of several cancers resulting in an increased interest in the role of naturally occurring dietary compounds in the efficacy of cancer chemoprevention [322]. Thus, the exploration of plant-based molecules as anti-cancer drugs is appropriate.

The history of Tamoxifen and its derivatives in the successful treatment of estrogen receptor (ER)+ve breast cancers are well documented. In the past Tamoxifen was successful in reducing breast cancer mortality rate in hormone receptor+ve breast cancer patients by up to a third and thus was the stronghold of endocrine treatment [323]. Clinical trials have indicated that aromatase inhibitors (AI) have improved efficacy compared with Tamoxifen for the treatment of post-menopausal hormone receptor+ve patients [324-327]. Additionally, the response rate for third generation AIs as first-line agents range from 30%–50% in ER+ve advanced breast cancer. [323]. Leading to these discoveries, and in an effort to capitalize on the advantages of both anti-aromatase and anti-estrogenic activity, many natural products have been tested for their ability to prevent and treat breast cancer, *in vivo* and *in vitro*. Table 4 summarizes plant based compounds that have been indicated for their potential as a prevention or treatment in breast cancer. This list is not exhaustive; however it does capture the extracts studied to date according to activity in cell lines and animal models and represents the most common types of breast cancer. In addition to those listed within Table 4, soy-based extracts, curcumin and piperine have been studied and we will discuss these in detail as the most promising plant based targets in the prevention, treatment and progression of breast cancer.
