Breast cancer therapies have made significant strides in improving survival for patients over the past decades. However, recurrence and drug resistance continue to challenge long-term recurrence-free and overall survival rates. Mounting evidence supports the cancer stem cell model in which the existence of a small population of
breast cancer stem cells (BCSCs) within the
tumor enables these cells to evade conventional
therapies and repopulate the
tumor, giving rise to more aggressive, recurrent
tumors. Thus, successful
breast cancer therapy would need to target these BCSCs, as well the
tumor bulk cells. Since the Women's Health Initiative study reported an increased risk of
breast cancer with the use of conventional
hormone replacement therapy in postmenopausal women, many have turned their attention to
phytoestrogens as a natural alternative.
Phytoestrogens are plant compounds that share structural similarities with human
estrogens and can bind to the
estrogen receptors to alter the endocrine responses. Recent studies have found that
phytoestrogens can also target BCSCs and have the potential to
complement conventional
therapy eradicating BCSCs. This review summarized the latest findings of different
phytoestrogens and their effect on BCSCs, along with their mechanisms of action, including selective
estrogen receptor binding and inhibition of molecular pathways used by BCSCs. The latest results of
phytoestrogens in clinical trials are also discussed to further evaluate the use of
phytoestrogen in the treatment and prevention of
breast cancer.