While mammograph can only detect breast cancer that is visible that mean has been growing in the body for over 10 year what else can we do to early detect and predict better outcome of breast cancer in the 20th century? Mammographic density is an evaluating tool in breast cancer risk because of the circulating RANKL (receptor activator of nuclear factor-kB) and soluble sRANK ligand. The RANKL are influenced by progesterone. The study suggest that reducing the high level progesterone level might reduce the high risk cancer in dense breasts. BDNF might be influenced by estrogen level.
The chance of cancer rate for breast cancer is 1:4 for women. Two things have been related to development of cancer: chronic inflammation and hormonal imbalance but may there is more.
BRK (non receptor thyrosine kinase) was found to be over expressed in 85% human invasive ductal breast tumor and there is a correlation between BRK and ER alpha. In addition, the survival of ER positive breast cancer patients is poor where there is high level of BRK.
Investigation in preventing breast cancer brain metastases are still not completely understood but studies suggest that the correlation between the Estrogen (E2) upregulation of brain derived neurotrophic factor (BDNF) on astrocytes and activation of tropomyosin kinase receptor B (TrkB) because ERα+ reactive astrocytes were found at early and late stages of brain metastasis. The treatment implications suggest that E2 depletion or TrkB inhibitors might delay the metastasis development.
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.
Nat Commun. 2019 Apr 3;10(1):1522. doi: 10.1038/s41467-019-09320-9.Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Zhou Y1, Gerrard DL2, Wang J3, Li T1, Yang Y1, Fritz AJ4, Rajendran M5,6,7,8, Fu X5,6,7,8, Schiff R5,6,7,8, Lin S9, Frietze S10, Jin VX11. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/?term=Temporal+dynamic+reorganization+of+3D+chromatin+architecture+in+hormone-induced+breast+cancer+and+endocrine+resistance
Oncogene. 2019 Jun;38(24):4685-4699. doi: 10.1038/s41388-019-0756-z. Epub 2019 Feb 22. Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases. Retrieved fromhttps://www.ncbi.nlm.nih.gov/pubmed/?term=.+Estradiol+induces+BDNF%2FTrkB+signaling+in+triple-negative+breast+cancer+to+promote+brain+metastases.
Estrogen receptor signaling regulates the expression of the breast tumor kinase in breast cancer cells.Miah S1, Bagu E1, Goel R1, Ogunbolude Y1, Dai C1, Ward A2, Vizeacoumar FS3, Davies G4, Vizeacoumar FJ2,3,5, Anderson D1,2, Lukong KE6. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30651078
Cancer Prev Res (Phila). 2018 Dec;11(12):789-796. doi: 10.1158/1940-6207.CAPR-18-0199. Epub 2018 Oct 23. Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal Women. Toriola AT1, Appleton CM2, Zong X3, Luo J3, Weilbaecher K4, Tamimi RM5, Colditz GA3. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30352839
BMC Cancer. 2019 Jan 16;19(1):78. doi: 10.1186/s12885-018-5186-8.Estrogen receptor signaling regulates the expression of the breast tumor kinase in breast cancer cells. Miah S1, Bagu E1, Goel R1, Ogunbolude Y1, Dai C1, Ward A2, Vizeacoumar FS3, Davies G4, Vizeacoumar FJ2,3,5, Anderson D1,2, Lukong KE6. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30651078