The Role of Estrogen in the Development of Breast Cancer

Breast cancer is a hormone-dependent disease that relies on the mitogenic effect of estrogen to increase tumorigenesis and tumor growth. Clinically significant levels of estrogen-α receptor (ERα) expression are seen in 80% of human breast cancers, whereas progesterone receptor is expressed in 55% of human breast cancers. These data are one of the bases for the development of endocrine therapy. Endocrine therapy is therapy that targets the pathway and synthesis of estrogen, by blocking it via receptors, reducing circulating levels of estrogen, or suppressing estrogen synthesis in the tissues of women diagnosed with breast cancer.


Introduction
Cancer is one of the most dangerous diseases.
Each year there are an estimated 9 million new cases and in develope d countries, it is ranke d second as the cause of human death. Cancer is also a 10% cause of death globally, therefore  and also through the lymphatic channels to invasion of blood vessels and spread to the lungs, bones, liver, pleura and adrenals 6 .
Breast cancer can generally be detected from a lump in one breast. The most common occurre n ce is a lump over the outer quadrant of the breast.
Reddish nipples, such as eroded, can also be a sign of breast cancer. Other characteristics are bleeding from the nipple or discharge from the nipple that is not cause d by lactation or pregna nc y and a change in the size of one part of the breast 7 .
Epide miolo gically, the incidence of breast cancer is high in North Europe and North America. Southern Europe and South America are areas of moderate incidence while low incidence occurs in Asia and Africa. China, althoug h included in the low incidence area, in large and medium cities, has a higher incidence than in rural and inland areas. This shows that in addition to genetics, environme ntal factors have an effect on one's susceptibility to breast cancer 6 .

Risk factors for breast cancer
Currently, it is known that the factors that This also occurs in women who are nullipariti c.
Women who are nulliparise d because they do not experience a pregnancy period that can stop a woman's exposure to estrogen, will be expose d to more estrogen than women who have experience d pregnancy in their lives 8,9,10,11 .
In obese women, more estrogen levels were   ERα and ER β are found in normal breast cells, but the site where ERβ is found is wider than ERα.
In mouse breast glands and human breast cells, ERβ is found in epithelial cells and stromal cells.

Estrogen receptors on the membrane
Estroge n receptors are also known to exist on membrane s other than the nucleus. mER is ofte n localized to caveolin-rich areas of the plasma membrane, particularly in endothelial cells.
Binding of estrogens to receptors on the membrane can regulate growth factor receptors and ER signal transduction pathways, which in turn can activate signal cascades such as MAP K.
This activation pathway is an integration of the activation pathway between the estrogen signal transduction pathway and growth factor 21 .

G-protein estrogen receptor (Gper)
Previous GPER1 also plays a role in activating the expression of genes related to NF-κB. NF-κB is a transcription factor that is redox sensitive. The stimulation of GPER1 causes the activation of NF -κB which translocates to the nucleus, binds to promoters in tarfet genes, and regulates the expression of genes that play a role in proliferatio n and migration through activation of Akt and the ERK cascade 13 .
The role of GPER1 in breast cancer metastasis that is ER negative indicates the secretion of IL-8, an interleukin that plays a role in cance r metastasis, is increasing. This occurs due to the interaction of estrogen with GPER1. IL-8 will then activate the CXCR1 receptor, a G protein that is thought to play an important role in metastasis and breast cancer invasion 13 .

Conclusion
The hormone estrogen is an importa n t