What Are Estrogen Receptors?
Receptors are proteins inside the target cell or on its surface that receive a chemical signal.
Estrogen is an important hormone responsible for various female characteristics in the body, including the growth and development of breasts (or mammary glands).
Estrogen Receptors (ERs) are a type of steroid receptors that attach to estrogen in the blood and regulate the growth and multiplication of cells in the breast. These receptors pick up signals from the hormones and encourage cell growth.
In the case of breast cancer, this growth is uncontrollable and eventually becomes cancerous.
Types of Breast Cancer
Based on the presence or absence of estrogen receptors in breast cancer cells, there are two types of breast cancers:
ER-positive
A cancer is called estrogen-receptor-positive (or ER-positive) if it has receptors for estrogen. The cancer cells receive signals from estrogen and grow in response to it.
ER-positive is the most common form of breast cancer - around 80% of breast cancers are ER-positive.
Anti-estrogen medications can prevent the growth of these cancer cells.
ER-negative
Breast cancer cells that do not have estrogen receptors are known as estrogen-receptor-negative (or ER-negative) cancers.
ER-negative breast cancer is less common and more challenging to treat. It also often has poor treatment outcomes.
Knowing whether breast cancer is ER-positive or ER-negative helps doctors plan the appropriate treatment.
Why Should Breast Cancer Be Tested For Hormone Receptors?
Every patient with a breast cancer diagnosis undergoes a hormone receptor evaluation that helps determine if the cancer cells have receptors for estrogen and progesterone.
About 2 out of every 3 breast cancer cases test positive for hormone receptors.
Testing breast cancer cells for hormone receptors is important to decide whether hormonal therapy will be an effective course of treatment.
Hormone therapy involves reducing the estrogen levels in the body or blocking the cells from responding to estrogen.
Only if the cancer is ER-positive, hormone therapy will work.
This makes ER-negative cancers difficult to treat; non-hormonal treatments are used for these cancers.
Genetic Factors Increasing The Risk For ER-Negative Breast Cancer
The BRCA2 Gene
The BRCA2 gene provides instructions for producing a protein that acts as a tumor suppressor (proteins that prevent cells from dividing uncontrollably and rapidly).
The BRCA2 gene is also involved in repairing damaged DNA.
Changes in the BRCA2 gene can increase the risk of different types of cancers, including breast cancer.
Most women with BRCA2 mutations tend to develop ER-positive breast cancer. However, the prognosis may be worse for these women than for those with ER-negative breast cancer carrying BRCA2 mutations.
The MDM4 Gene
The MDM4 gene is located on chromosome 1 and produces the MDM4 protein, which regulates a tumor suppressor protein called the p53.
Changes in this gene can affect the protein produced, which in turn interferes with the tumor suppressor activity of p53.
When this happens, it can lead to uncontrolled cell growth resulting in cancer cell formation.
The ZNF365 Gene
The ZNF365 gene contains instructions to produce the Zinc Finger Protein 365. This protein plays a role in repairing DNA damage. Changes in this gene increase the risk of breast cancer.
A change in the ZNF365 gene, called 19p13.1, has been linked to ER-negative breast cancer in individuals with changes in their BRCA1 and BRCA2 genes.
Non-genetic Factors Influencing ER-negative Breast Cancer Risk
Race: There is a higher incidence of ER-negative breast cancers in women of African ancestry.
Obesity: Pre-menopausal and menopausal women who are overweight or obese are at an increased risk of developing ER-negative breast cancer.
Alcohol consumption: Increased alcohol intake increases the risk of ER-negative breast cancer.
Younger Age: Hormone receptor-negative cancer is more commonly seen in women around 40 years of age who haven’t attained menopause
Recommendations To Reduce Risk Of ER-negative Breast Cancer
Regular Physical Activity
Physically active women who have a healthy weight and lead a healthy lifestyle have a reduced risk of developing ER-negative breast cancer.
Limited Alcohol Consumption
Even low levels of alcohol intake can increase the risk of breast cancer. The ideal upper limit for alcohol consumption to lower breast cancer risk is one drink a day (12-14 grams of alcohol).
Plant-based Diet
Plant-based diets are packed with fiber, vitamins, and minerals. Fiber helps eliminate excess estrogen (a risk factor for breast cancer). Vitamin C, A, and selenium also play a role in lowering cancer risk.
A 2013 study that followed approximately 30,000 post-menopausal women with no history of breast cancer for 7 years showed that following these three recommendations resulted in a 62% decreased risk of breast cancer.
Genetic test for BRCA Mutations
The BRCA genetic test is a blood test that analyses DNA to detect the presence of harmful changes (mutations) in the BRCA1 and BRCA2 genes. Individuals with these mutations are at a high risk of developing breast cancer. Routine testing for these genes in individuals at high risk is recommended.
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Summary
- Depending on the presence or absence of estrogen receptors on breast cancer cells, breast cancer can be classified as ER-positive or ER-negative.
- ER-positive breast cancers form 80% of the total breast cancer cases and are easier to treat with hormonal treatments. ER-negative breast cancers do not respond to hormone therapies.
- Knowing the ER status of breast cancer helps the doctor determine the treatment plan for a patient.
- The prognosis for women carrying BRCA2 mutations and diagnosed with ER-positive breast cancer is poorer than for those with ER-negative breast cancer.
- Changes in the MDM4 gene can interfere with the tumor suppressor activity of p53 protein, resulting in an increased risk for breast cancer.
- Other factors like race, menopausal status, and alcohol intake influence a woman’s risk of developing ER-negative breast cancer.
- Eating a healthy and nutritious plant-based diet, limiting alcohol intake, and being physically active can reduce the risk of ER-negative breast cancer.
- BRCA genetic testing can help you assess the risk more precisely and take preventive measures.
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389841/
- https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html
- https://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive
- https://www.breastcancer.org/symptoms/diagnosis/hormone_status
- https://academic.oup.com/jmcb/article/11/3/231/5301298
- https://academic.oup.com/carcin/article/30/11/1910/2629508
- https://cancer.ucsf.edu/sites/cancer.ucsf.edu/files/_docs/crc/nutrition_breast.pdf
