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Estradiol (E2) is a type of estrogen steroid hormone. It is one of the female sex hormones and is responsible for managing the reproductive cycle. It also plays a major role in the reproductive health of a woman.

Both men and women have natural estradiol hormones in the body. A woman’s body produces more estradiol than a man’s.

The Role of Estradiol In Reproductive Life

What Happens When Estradiol Levels Are Low?

What Happens When Estradiol Levels Are High?

Estradiol Levels and Breast Cancer Risk

According to the American Cancer Society, the incidence rate of breast cancer has been increasing by 0.5% every year. Breast cancer is the second leading cause of cancer deaths in women in the United States. 

Excess estradiol in the body interacts with two Estrogen Receptors (ERs) - ERα and ERβ. Estrogen receptors are proteins that get activated on exposure to estrogen. These ERs are responsible for controlling a variety of genes and their functionalities. 

The ERα interacts directly with DNA repair proteins with varying impacts on DNA repair mechanisms. In some cases, it can result in abnormal cell production and multiplication, leading to breast cancer. 

A 2002 study analyzed the effects of serum E2 levels and the risk of breast cancer. 7290 postmenopausal women under the age of 80 were included in the study. The study records that women with estradiol levels higher than 10 pmol/L had a 6.8 fold higher risk for breast cancer

According to a 2001 study, postmenopausal women with higher estradiol levels (>12 pmol/L) had a 2.07 fold higher risk for invasive breast cancer

Another study explored how estrogen metabolism influences breast cancer risk. 1298 postmenopausal women with cases of breast cancer and 1524 matched controls were considered for the study. The study reported that total estrogen levels were positively and strongly associated with breast cancer risk. 

Genetic Factors Influencing Estradiol Plasma Levels And Breast Cancer Risk

The CYP19A1 Gene 

The CYP19A1 gene produces an enzyme called aromatase. Aromatase helps convert androgens (hormones associated with male traits) to different forms of female hormones (estrogen).

This enzyme is very important in the production and maintenance of female reproductive hormones. This enzyme is also needed for the last step of estrogen production in the body (biosynthesis). 

Certain types of CYP19A1 gene can lead to excess production of estradiol, leading to an increased risk for breast cancer. 

Increased aromatase levels lead to a lower survival rate in people with Estrogen Receptor-Positive Breast Cancer. 

Family History

Women who have increased estradiol levels in the body and a family history of breast cancer (first or second-degree relatives with a past or present cancer diagnosis) are at higher risk. 

Non-Genetic Factors Influencing Estradiol Plasma Levels And Breast Cancer Risk

Gender: 99 out of 100 breast cancer cases occur in women, making the female sex a risk factor for breast cancer.

Hormone Replacement Therapy: Hormone Replacement Therapy (HRT) is recommended for women during their menopausal period to help manage the symptoms better. There are two common types of HRT procedures recommended:

Combination HRT increases the levels of estradiol in the body. This can increase the risk of breast cancer by up to 75%. 

Estrogen-only HRT also increases estradiol levels, but the effects are seen only after 10 years

According to a 2005 study, Hormone Replacement Therapy (HRT) remains the most important risk factor for ER+ breast cancer

Reproductive cycle: Girls who get their periods before 12 and women who don’t experience menopause before 55 are more exposed to estrogen. This increases estradiol levels in the body and can increase the risk for breast cancer

Breastfeeding duration: Women who breastfeed have higher levels of prolactin. Higher prolactin levels lead to lower estradiol levels. Hence, women who breastfeed for a longer duration may be protected against breast cancer

Gut health: The human Gastrointestinal Tract (GI tract) contains billions of bacteria, viruses, and other microorganisms that keep the body healthy. 

Estradiol is produced in the adrenal glands, ovaries, and adipose tissues. It circulates through the bloodstream and is converted into usable forms in the liver. The remaining estradiol is sent out to the bile and the urinary tract. Certain bacterial species can pull out this estradiol from the bile and send it back to circulation. This leads to increased estradiol levels and an increased risk of breast cancer. 

Obesity: According to a 2010 study, in postmenopausal women, obesity was associated with increased levels of estradiol. Obese women had higher levels of estradiol when compared to non-obese women. This increases their risk for breast cancer too. 

Recommendations to lower Estradiol Plasma Levels

Genetic Testing

Genetic testing can help assess your breast cancer risk by analyzing your BRCA genes. It also helps analyze other risk factors like estrogen exposure. You can talk to a genetic counselor to get more information on this. 

Be Aware of Exposure to Chemicals

Certain chemicals used in making everyday products can cause problems in the endocrine system. These are called Endocrine Disrupting Chemicals (EDCs). 

Some of these chemicals are:

Most plastics used at home have one or more of these chemicals in them. A study reported that younger people who have a higher exposure to BPA and have early puberty show higher estradiol levels in the body.  

In another study, female rats that were exposed to higher levels of Endocrine Disrupting Chemicals (EDCs) showed increased levels of estradiol

Switching over to more natural crockeries, tableware, and cookware can help bring down the risk of increased estradiol levels. 

Maintain A Healthy Weight

Maintaining a healthy weight can help reduce estradiol fluctuation in the body and decrease the risk of breast cancer. 

Regular Screening For Breast Cancer During Menopause

Women’s natural estradiol levels fluctuate extremely during menopause. Perimenopausal women (women in menopause) may have up to two times the normal estradiol levels

During this period, it will help if you are regularly screened for breast cancer. This will help with early diagnosis and a better prognosis.


  1. Estradiol is a major type of estrogen steroid hormone responsible for maintaining the female reproductive system. While both men and women produce estradiol in their bodies, the levels are higher in women than in men.
  2. Higher levels of estradiol in the body are associated with an increased risk of breast cancer and uterine cancer. 
  3. The CYP19A1 gene produces an enzyme called aromatase. This enzyme converts androgens to estrogens. Certain changes in this gene can increase the risk for breast cancer.
  4. Some women may also have a family history of breast cancer and increased estradiol levels. The combination of both further increases the risk of breast cancer.
  5. Women who opt for Hormone Replacement Therapy have increased estradiol levels in the body. This increases the risk of breast cancer.
  6. Girls who reach puberty early and women with delayed menopause are more exposed to estradiol in their lifetimes and have a higher risk for breast cancer.
  7. Certain bacteria in the gut may increase the levels of circulating estradiol in the body. This also increases the risk of breast cancer.
  8. Genetic testing can help assess your risk for breast cancer. It analyzes your BRCA genes and other factors that contribute to breast cancer risk.
  9. Losing weight and regular breast cancer screening during menopause can help you manage breast cancer risk more effectively.
  10. Staying away from chemicals like BPA and DDTs brings down estradiol levels in the body.


What is Menopausal Hormone Therapy?

Menopausal Hormone Therapy (MHT) is widely prescribed for postmenopausal women to ease symptoms of menopause such as hot flashes, vaginal dryness, and sleep disturbances. 

There are two types of Hormone Replacement Therapy (HRT):

According to recent research, it has been found that Combination Menopausal Hormone Replacement Therapy increases the risk of breast cancer by 75%, even when administered for a very short time. In contrast, estrogen-only hormone therapy increases the risk of breast cancer only when used for longer than 10 years.

What Are The Health Effects Of Menopausal Hormone Therapy?

How Does Genetics Influence Breast Cancer Risk with Menopausal Hormone Therapy?

Some genes promote higher growth of estrogen receptors during menopausal hormone therapy. This increases the risk of ER-positive breast cancer. 

The CYP19A1 Gene

The CYP19A1 gene contains instructions for the production of a protein involved in estrogen biosynthesis. 

Certain changes in this gene are associated with poor treatment outcomes of hormone therapy in women in the early stages of ER-positive breast cancer. 

The POMP Gene

The POMP gene contains instructions for the production of proteasome maturation protein. A study revealed two regions in the POMP gene showing interaction with hormone therapy that increased the risk of breast cancer.

Non-genetics Factors that Influence Breast Cancer Risk with Menopausal Hormone Therapy

Obesity: According to a study published in Cancer Epidemiology Biomarkers in 2008, both types of hormone therapy are associated with breast cancer risk. The risk is further influenced by the body mass of the individual and the clinical characteristics of the tumors

In women with BMI <25 kg/m2, estrogen therapy was associated with a 60% increase in breast cancer risk after 10 years of the therapy. The risk increased with combined therapy. Combined therapy with estrogen and progesterone was also strongly associated with ER-positive tumors.

Alcohol consumption: Drinking alcohol while taking postmenopausal hormone replacement therapy can increase the risk of developing breast cancer. This is because drinking alcohol increases estrogen levels, and when combined with the estrogen in hormone therapy, it significantly increases estrogen in a woman’s body.

A study was conducted to analyze drinking habits and hormone therapy use in over 5,000 Danish women for over 20 years. The researchers found that postmenopausal women who took Hormone Replacement Therapy (HRT) and drank 1 or 2 alcoholic drinks per day had three times higher risk of breast cancer than women who did not drink and were not taking HRT. Also, postmenopausal women taking HRT who drank more than 2 alcoholic drinks per day had a five times higher risk of breast cancer than women who did not drink and were not taking HRT.

Smoking: Smoking has been associated with an increased risk of breast cancer in women. This risk is much higher for women who smoke while taking postmenopausal hormone therapy.



What is Estrogen Receptor-Positive Breast Cancer? 

Estrogen is the female sex hormone responsible for the growth, development, and regulation of the female reproductive system and secondary sex organs. 

The cells that respond to this hormone contain proteins that bind to it and bring about the required effect. These proteins are known as estrogen receptors and are found in female reproductive tissues and cancer cells. 

Breast cancers that grow in response to estrogen due to the presence of estrogen receptors are known as estrogen receptor-positive or ER-positive breast cancer. 

These cancers grow slower than ER-negative cancers and account for 80% of all breast cancers. 

They also have better treatment outcomes in the short term but tend to relapse after years of treatment.

Testing For Hormone Receptors In Breast Cancer

In ER-positive cancers, the growth of cancer cells is estrogen-dependent. 

So, hormone therapy drugs can be used to lower estrogen levels in the body or prevent estrogen from affecting breast cancer cells.

 Knowing the hormone receptor status of breast cancers can help doctors figure out the ideal treatment plan for the patient. 

Risk For Er Positive Cancers: Genetic Factors

The BRCA Genes

Women who are carriers of the BRCA1 gene mutations are more likely to develop ER-positive breast cancer as they age. 

10-36% of breast cancer cases in people with BRCA1 gene mutations are ER-positive breast cancers.

According to a study, most women with BRCA2 mutations develop ER-positive breast cancer and the treatment outcome for these women may be poorer than BRCA2 carriers having ER-negative breast cancer.

The CYP19A1 Gene

Estrogen exposure plays a significant role in breast cancer. The CYP19A1 or Cytochrome P-450, family 19, subfamily A, contains instructions for the production of aromatase, an enzyme that regulates the final step in the production of estrogen in the body. 

Abnormal changes in the CYP19A1 gene are significantly associated with different levels of circulating estrogens

Treatment with Aromatase inhibitor drugs that suppress estrogen production yield better outcomes in ER-positive breast cancer patients with mutations in their  CYP19A1 gene. 

The ESR1 Gene

The ESR1 gene contains instructions for the production of estrogen receptor alpha (a type of estrogen receptor). 

Certain changes in the ESR1 gene increase the resistance of cancer cells to hormonal therapy, the standard treatment plan for ER-positive cancers.

Non-genetic Factors

- Age: Older women tend to have a higher amount of estrogen receptors, increasing their risk for ER-positive breast cancer.

- Lifetime exposure to estrogen: Women who begin menstruating early, attain menopause late, or do not have children are at a higher risk of ER-positive breast cancer due to longer lifetime exposure to estrogen.

- Alcohol consumption: Alcohol can increase the levels of estrogen and other hormones associated with ER-positive breast cancer. It increases the likelihood of developing ER-positive breast cancer.

- Hormone treatment post-menopause: Women who take hormone therapy after menopause are more likely to develop ER-positive breast cancer.

- Higher BMI (Body Mass Index): Obesity amplifies the risk for ER-positive breast cancer because adipose tissue acts as the major reservoir for estrogen production after menopause.

- History of Breast Lesions: Women with a history of benign growing breast lesions have an increased risk of ER-positive breast cancer.

Recommendations To Reduce Risk Of ER-positive Breast Cancer


Some foods like soya, red meat, and dairy have chemicals that function like estrogens. 

For this reason, individuals with a high risk of ER-positive breast cancer must avoid them. 

They can instead include cancer-fighting foods such as fresh fruits and vegetables (apples, blueberries, asparagus, carrots, tomatoes, etc.), foods rich in fiber (whole grains, oats, etc.), and healthy fats like omega-3 and omega-6 fatty acids. 

If you are at high risk of developing ER-positive breast cancer, you must reduce your body fat and limit or completely avoid saturated fats, alcohol, and red meat. 


Physical activity and regular exercise reduce ER-positive breast cancer risk.


Aromatase-inhibitor drugs are effective in preventing ER-positive breast cancer.

Note: Aromatase inhibitors should be consumed only upon your medical practitioner's advice. 

BRCA Screening

A BRCA genetic test can help find out your risk for ER-positive breast cancer. Routine breast cancer screening is recommended for those found to be at high risk based on their genetic profile.



  1. Breast cancers that grow in response to estrogen are known as Estrogen Receptor-positive or ER-positive breast cancers.
  2. ER-positive breast cancers are more common and constitute around 80% of all diagnosed breast cancer cases.
  3. Hormone therapy and drugs like Tamoxifen and aromatase inhibitors are used to treat ER-Positive breast cancers.
  4. Abnormal changes in genes like BRCA1, BRCA2, CYP1A1, and ESR1 are associated with an increased risk of developing ER-positive cancer and a poorer prognosis.
  5. A few non-genetic factors that increase one's risk of developing ER-positive breast cancer include older age (above 50), longer lifetime exposure to estrogen, alcohol consumption, higher BMI, and history of benign breast lesions.
  6. You can reduce your risk of ER-positive breast cancer by following a healthy diet loaded with fruits and vegetables, exercising regularly, and going for regular screenings.


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:


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. 


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.



  1. Depending on the presence or absence of estrogen receptors on breast cancer cells, breast cancer can be classified as ER-positive or ER-negative.
  2. 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.
  3. Knowing the ER status of breast cancer helps the doctor determine the treatment plan for a patient.
  4. The prognosis for women carrying BRCA2 mutations and diagnosed with ER-positive breast cancer is poorer than for those with ER-negative breast cancer. 
  5. Changes in the MDM4 gene can interfere with the tumor suppressor activity of p53 protein, resulting in an increased risk for breast cancer. 
  6. Other factors like race, menopausal status, and alcohol intake influence a woman’s risk of developing ER-negative breast cancer.
  7. Eating a healthy and nutritious plant-based diet, limiting alcohol intake, and being physically active can reduce the risk of ER-negative breast cancer.
  8. BRCA genetic testing can help you assess the risk more precisely and take preventive measures.


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