The Role of Estrogen in Breast Cancer: How ER-Positive Tumors Respond to Hormonal Signals

Breast cancer is a widely present cancer among women worldwide. Breast cancer is caused by development of abnormal breast cells that spread and develop into tumors. Tumors have the potential to grow throughout the body and become lethal if ignored. However, many of the women do not experience any symptoms in the early stages of the cancer.

Risk factors

• People assigned female at birth

• Menarche before the age of 12 

• Menopause after the age of 55

• Women who are not pregnant

• Alcohol 

• Obesity

• Exposure to radiation

• Personal / family history of breast cancer

Symptoms of breast cancer

• Thickening or lump in the breast, frequently without any pain

• Changes to the breast's size, shape, or appearance

• Dimpling, redness, pitting, or other skin abnormalities

• Alteration in the appearance of the nipple or the skin (areola)

• Abnormal or bloody nipple fluid.

Understanding the connection between estrogen and breast cancer biology

The formation of estrogen is a complex reaction that includes the cascade of reactions from cholesterol synthesis to pregnenolone, which further changes into androgens that at least transform into estrogen. The potent biologically active form of estrogen is called estradiol.

The various steps involved in the production of estrogen metabolites are hydroxylation with further methylation and sulfation. These reactions take place in the presence of the enzyme cytochrome P450. The balance in the formation of various kinds of metabolites and the pathways they are produced can influence the risk for breast cancer.

Estrogen produced within the body (endogenous) and derived from external sources (exogenous) such as hormone replacement therapy (HRT), contributes to an increased risk of breast cancer. Long-term exposure to estrogen, either through early menarche, late menopause, nulliparity, or HRT use, is linked with an elevated risk of developing hormone receptor-positive breast cancer. 

Estrogen alpha and estrogen beta are the two types of receptors that are found in the majority of breast cancers. The hormone receptor-positive tumors are responsible for most of the types. When the estrogen binds to the ER receptors, they undergo conformational changes, and any changes in the signaling pathway will cause uncontrolled cell growth and trigger tumor development.

Breast cancer with hormone receptor positivity

It is defined by the presence of estrogen and progesterone receptors. About 70–80% of all cases of breast cancer are hormone receptor-positive. The  Estrogen receptor -positive breast cancer can be treated by using the targeted approaches against estrogen receptor blockers.

Treatment for ER-Positive Breast cancer

1. Selective estrogen receptor modulators: 

They attach to the estrogen receptors and effectively stop the estrogen from binding at its site. Depending on where they are expressed in the body, SERMs have the ability to both mimic and block the effects of estrogen. They do this by preventing estrogen from attaching to its receptor. Tamoxifen mimics and functions similarly to the estrogen in the uterus and bones but inhibits the actions of estrogen in breast tissue. Faslodex injection contains the active compound fulvestrant that is an estrogen receptor antagonist that is used to treat post menopausal women with estrogen receptor positive breast cancer. 

2. Aromatase inhibitors: 

The specific type of enzyme responsible for the inhibition of the hormone estrogen is aromatase.  Because the ovaries of premenopausal women build too much aromatase, aromatase inhibitors are generally utilized in postmenopausal women.

3. Chemotherapy 

• Neoadjuvant Chemotherapy: Chemotherapy may be administered before surgery to shrink the tumor. 

• Adjuvant Chemotherapy: Chemotherapy can be given after surgery to eradicate any remaining breast cancer cells.

4. Breast-Conserving Surgery: 

This method includes radiation therapy to the breast after the tumor and a margin of surrounding healthy tissue are removed during the treatment (lumpectomy).

5. Mastectomy: 

This procedure involves the removal of the total breast tissue and is used when breast-conserving surgery is not possible or desired. 

Conclusion

It is essential to identify and follow screening procedures at an early stage to reduce the risk of metastasis. Discussing the treatment approaches, developing a regimen that meets the individual needs is necessary.