While HRT (hormone replacement therapy) has been attributed pro cancerous effect, the phytoestrogen seem to exhibit opposite effects. Phytoestrogen are plant-based derived estrogen that exhibit estrogenic activity that might become a better therapeutic agents for postmenopausal hormonal treatment because of tumor protective properties.  There are two main nuclear estrogen receptors (ER) in the body ER alpha and ER beta. Many disease are related to the 17 beta estradiol which act through estrogen receptors ER alpha and beta. The important role of 17 beta estradiol is the rapid signaling via pathways of ERs such as G protein couple Er1 (GPR30) and this pathway is under investigation as a prognostic indicator and therapeutic tool.

The role of ER alpha and ER beta expressed by phytoestrogen are expressed in cardiovascular protection and cancer protection. ER alpha and ER beta signal in opposite ways with ER beta acting as cancer protection. In the investigation of MCF-7 (human estrogen receptor positive and progesterone receptor positive breast cancer cells) it was found that phytoestrogen like resveratrol, quercetin and genistein inhibited the cellular proliferation.

Phytoestrogen (apigenin, quercetin, genistein) bind to estrogen receptor (ER) and appear to inhibit the breast cell cancer including HER positive. Some studies show that high dose of apigenin does not display estrogen like activity and suggest to suppress 17 alpha estradiol. Phytoestrogene like pinoresional (found in virgin olive oil) was found to be pro oxidant, antiproliferative, antitumor and acts as a chemopreventative compound. Another phytoestrogen like Arctigenin (lignin from Arctium lappa) helps with menopausal symptoms, heart disease and bone benefits. Studies show that arctigenin exhibit anti cancerous effects by up steam signaling pathways in MMP-9 and urokinase plasminogen activator (uPA) with inhibiting NF-k, MAPK (ERK1/2 and Jnk ½) regardless of ER expression.

Mol Biol Rep. 2015 Jan;42(1):167-77. doi: 10.1007/s11033-014-3756-7. Epub 2014 Sep 25.

Mol Biol Rep. 2015 Jan;42(1):167-77. doi: 10.1007/s11033-014-3756-7. Epub 2014 Sep 25. The effect of Momordica charantia intake on the estrogen receptors ESRα/ESRβ gene levels and apoptosis on uterine tissue in ovariectomy rats. Cevik O1, Akpinar H, Oba R, Cilingir OT, Ozdemir ZN, Cetinel S, Yoldemir T. Retrieved fromhttps://www.ncbi.nlm.nih.gov/pubmed/?term=The+effect+of+Momordica+charantia+intake+on+the+estrogen+receptors+ESR%CE%B1%2FESR%CE%B2+gene+levels+and+apoptosis+on+uterine+tissue+in+ovariectomy+rats

Toxicol Appl Pharmacol. 2017 Jun 15;325:61-70. doi: 10.1016/j.taap.2017.04.005. Epub 2017 Apr 7.Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation. Lecomte S1, Lelong M1, Bourgine G1, Efstathiou T2, Saligaut C1, Pakdel F3 Retrieved fromhttps://www.ncbi.nlm.nih.gov/pubmed/28396216

Asian Pac J Cancer Prev. 2014;15(21):9085-91. Phytoestrogen intake and risk of ovarian cancer: a meta- analysis of 10 observational studies. Qu XL1, Fang Y, Zhang M, Zhang YZ Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25422183

Chem Res Toxicol. 2011 Jan 14;24(1):6-19. doi: 10.1021/tx100231n. Epub 2010 Nov 5. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21053929