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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.

Summary

  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.

References

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.

Recommendations

Summary

Menstrual Cycle and Breast Cancer Risk

The year 2020 saw around 2.3 million women being diagnosed with breast cancer. As per the latest report from GLOBOCAN published in February 2021, breast cancer has surpassed lung cancer in being the most prevalent cancer type in the world.

Compared to the high risk of breast cancer in women, the risk of breast cancer in men is a minuscule 0.5-1%. A significant reason for the high risk and prevalence of breast cancer in women is attributed to the reproductive hormone, i.e., estrogen and progesterone fluctuations

To understand the relationship between the menstrual cycle and breast cancer risk, we must know that the most common breast cancers are hormone receptor-positive breast cancers - the cancer cells have estrogen or progesterone or both types of receptors. 

These breast cancer cells grow and multiply when exposed to estrogen and progesterone. However, a few types of breast cancer are hormone-receptor negative, which means that these breast cancer cells have no hormone receptor cells and are often more challenging to treat.

Every girl who begins her menstrual cycle has a 5% risk of developing breast cancer in her lifetime. This is because the mammary glands begin forming and remain under the influence of different reproductive hormones as soon as a girl hits puberty, during pregnancy, and even during lactation. 

The constant fluctuations in estrogen and progesterone levels during a woman’s reproductive life affect the mammary gland function, cell growth, turnover, and immune cells like the regulatory T cells and the macrophages. 

Together, these effects cause increased instability of the individual’s genome, increase their susceptibility to genetic mutations, reduce their immunity, and trigger breast cancer development. 

Menopause and Breast Cancer Risk

Menopause does not cause breast cancer, but the risk of developing breast cancer increases as the woman ages. According to statistics, a woman who attains menopause after 55 years of age has an increased risk of breast, ovarian, and uterine cancers

This risk is also greater if a woman starts menstruating before the age of 12 years. Therefore, the longer a woman’s reproductive life, the longer her breast tissue is exposed to hormonal fluctuations, increasing her risk for breast cancer.

It has been observed that postmenopausal women have a lower risk of breast cancer compared to premenopausal women of the same age and with the same childbearing pattern. Also, the risk of breast cancer increases by 3% for each year that menopause gets delayed. 

So, women who attained menopause later than 55 years of age had a 30% increased risk of breast cancer than women who reached menopause at 45 years of age. 

Postmenopausal breast cancer is known to be less aggressive than breast cancer that occurs in younger women. However, obesity or increased weight is an independent risk factor for breast cancer in menopausal women. This is because serum estradiol (a form of the female hormones estrogen) is increased in obese patients, triggering breast cancer development.  

Another study re-iterated the findings mentioned above, stating that lower age of menopause had a protective effect and reduced breast cancer risk compared to the higher age of the woman. This protective effect may be more substantial in leaner women.

Many women take combined hormone therapy to relieve menopausal symptoms like hot flashes and osteoporosis. This treatment is also called Hormone Replacement Therapy (HRT). 

In this therapy, estrogen and progesterone are combined and administered to postmenopausal women to help manage their symptoms. 

However, HRT increases a woman’s risk of developing breast cancer, stroke, heart attack, and blood clots.

How Genes Influence Postmenopausal Breast Cancer Risk

Genetics plays a significant role in the development of breast cancers. Around 5% to 10% of breast cancers occur when an abnormal gene is passed from the parent to the child. 

The most commonly inherited genes that lead to breast cancer are the BRCA1 and BRCA2 genes. However, genes that influence the risk of breast cancer in postmenopausal women include-  ESR1, PGR, XRCC1, VDR, CAT, CYP2C19, and XRCC3, among others.

ESR1 Gene

ESR1 or the Estrogen Receptor 1 gene provides instructions for the production of estrogen receptor production and ligand-activated transcription factor. These estrogen receptors play a role in growth, development, sexual development, and reproductive functions. Unfortunately, they also play a vital role in breast cancer development, endometrial cancer, and osteoporosis.

rs9340799 is a Single Nucleotide Polymorphism (SNP) in the ESR1 gene and located on chromosome 6. A study on Mexican women showed that women carrying the XbaI  (WT/G or G/G) ESR1 genotype have a 12.26 times greater risk of developing postmenopausal breast cancer than those carrying the WT/WT genotype. 

However, women with t or the wild type of XbaI had no association with breast cancer. Also, postmenopausal women who were both heterozygous and homozygous for XbaI had a strong association with breast cancer.

PGR Gene

PGR or Progesterone Receptor gene mediates the physiological effects of the hormone progesterone, which plays a vital role in the reproductive cycle in women.

rs10895068 is an SNP in the PGR gene, which is located on chromosome 11. Having two AA alleles or at least one A allele increases the risk of breast cancer in postmenopausal women by 2.5 times compared to those with the GG genotype. 

Recommendations To Reduce Post-Menopausal Breast Cancer Risk

Lifestyle changes can help reduce the risk of breast cancer in postmenopausal women. 

Gaining weight after menopause can increase a woman’s risk for breast cancer. One must maintain a healthy weight throughout their life to reduce the risk of cancer (According to The American Cancer Society)

Though the direct link between alcohol consumption and increased risk for breast cancer has not been established yet, consuming even lower amounts of alcohol can increase your risk for breast cancer.

Studies have shown that the longer a woman breastfeeds, the lower her risk for breast cancer. For example, researchers have found that for every 12 months that a woman breastfeeds, her risk for breast cancer decreased by 4.3% 

Women who opt for hormonal therapy after menopause must speak with their doctor as these therapies increase the risk for breast cancer. Ask for non-hormonal alternatives or short-term hormone therapy options to manage menopausal symptoms. 

Following a healthy diet low on red meat, processed foods, sugary foods, and fat can reduce your risk for breast cancer. However, the association between diet and breast cancer is still under research.

Smoking increases the risk for all types of cancer, including breast cancer. Therefore, women who are smokers must quit the habit to lower their risk of developing breast cancer post-menopause.

It is recommended that women with a familial history of breast cancer undergo genetic counseling.  This can help determine the course of action to reduce their risk and chances of developing breast cancer.

Routine doctor visits and breast exams are recommended for all women above the age of 35 years. Regular monitoring reduces the chances of late detection and improves prognosis.

Summary

References:

What is Smoked Meat?

Smoking is an ancient cooking technique that exposes meat to smoke and slow-cooks it for long hours. The smoke adds a flavor of its own to the meat and gives the cooked meat a unique taste that people love. 

This cooking technique dates back to the paleolithic era (old stone age). There are two reasons why meat is smoked.

  1. Certain chemicals like formaldehyde in smoke help preserve meat. Therefore, meat is smoked to increase its shelf life.
  2. Smoking creates a brown and crispy exterior to the meat and makes the meat taste better. Slow-cooking using smoke also makes meat juicer. 

Does Smoked Meat Cause DNA Damage?

One of the chemicals produced due to burning wood while smoking food is Polycyclic Aromatic Hydrocarbon (PAH). PAHs are carcinogenic (cancer-causing) agents. There are two ways PAH damages the DNA.

While people can be exposed to PAHs by inhaling cigarette smoke, staying in places with high air pollution, and through occupation exposure, consuming smoked meat is a direct form of dietary PAH exposure. 

When you cook fat-rich meat on an open fire, the fats and juices from meat splash on the fire and lead to smoke and flames. The PAH-rich smoke sticks to the meat, making the food carcinogenic.

A study analyzed the PAH content in different smoked foods. It was reported that meat smoked with natural wood had higher levels of carcinogenic PAHs than meat smoked using liquid smoke flavorings (artificial flavoring that can be used as a substitute for natural wood smoke). 

According to the study, smoked salmon had a range of PAH/kg of 86.6mg, and cooked ham had 29.8mg/kg of PAH. On the other hand, smoked shrimp had a low PAH/kg value of 9.3.

How Does Smoked Meat Consumption Affect Breast Cancer Risk?

Excess consumption of smoked meat can increase the risk of developing different kinds of cancer, including breast cancer. Smoked meat consumption is also associated with an increased mortality rate in breast cancer survivors.

A long-term study identified 1508 women with invasive breast cancer in 1996 and 1997. These women were monitored for approximately 17.6 years. Among these women, 237 died because of breast cancer. Researchers analyzed the average smoked meat intake in these women.

Women who consumed an excess of smoked meat in this group had a 31% higher mortality risk. 

According to the American Cancer Society, there are more than 3.8 million breast cancer survivors in the country, including those still in treatment and those who have completed treatment. These women can increase their survival rate by limiting the consumption of smoked meat. 

How Does Genetics Influence Breast Cancer Risk on Smoked Meat Consumption?

Changes in certain genes can increase or decrease a person’s risk for developing breast cancer on the consumption of smoked meat. 

CYP1A1 Gene 

The CYP1A1 gene (cytochrome P450 family 1 subfamily A member 1 gene) helps produce the CYP1A1 enzyme, part of the cytochrome P450 family of enzymes (CYP 450). This enzyme helps eliminate a variety of drugs and chemicals from the body. It also plays a role in the bioactivation of PAHs, converting them into a more toxic intermediary that can cause cancer.

rs1048943 is a  single nucleotide polymorphism or SNP in the CYP1A1 gene. It is associated with breast cancer risk. The A allele of this SNP is associated with excess consumption of smoked meat and an increased risk of breast cancer

AlleleImplications
AHigher risk of breast cancer with  higher lifetime intake of smoked meat
GRegular risk of breast cancer with  higher lifetime intake of smoked meat

CYP1B1 Gene

The CYP1B1 gene (cytochrome P450 family 1 subfamily B member 1 gene) helps produce the CYP1B1 enzyme. This enzyme also plays a role in eliminating various endogenous (internally produced) and exogenous (externally produced) hormones, lipids, chemicals, and drugs.

rs 10175338 is an  SNP in the CYP1B1 gene. It is associated with breast cancer risk. The T allele of this SNP is associated with excess consumption of smoked meat and an increased risk of breast cancer

AlleleImplications
THigher risk of breast cancer with  higher lifetime intake of smoked meat
GRegular risk of breast cancer with  higher lifetime intake of smoked meat

SULT1A1 Gene 

The SULT1A1 gene (Sulfotransferase 1A1 gene) helps produce the SULT1A1 enzyme. This enzyme plays a role in the sulfation of many drugs and chemicals, including PAHs.

People with the SULT1A1 His/His genotype of the SNP rs1042028 of this gene had an increased risk of breast cancer from consuming excess smoked meat than those with the SULT1A1 Arg/Arg genotype.

Tips To Cook Meat The Healthier Way To Reduce Breast Cancer Risk

Try Alternative Cooking Methods

Grilling, barbecuing, and smoking are just a few of the different ways of cooking meat. There are other alternate healthier cooking methods:

Choose Low-Fat/Lean-Cut Meat

Choose lean-cut meat over fat-rich meat when you want to smoke, grill, or barbecue it. This way, excess fat will not drip over the fire and trigger smoke and flames. If you get a fat-rich portion of meat, you can trim the fat edges before cooking. 

Some people also pre-cook meat before smoking it. This way, the excess fat is pre-cooked and does not drip down much.

Do Not Consume Blackened (Charred) Bits

Do not consume parts of the meat that are charred because of smoking. These contain the most amounts of PAH. You can trim the charred parts before you serve the meat on the table.

Use Thermometers To Avoid Overcooking

Overcooking is one reason why meat gets charred or overburnt while smoking or grilling it. Use a thermometer to immediately remove the meat from heat after it is cooked to avoid charring. 

Include Fresh Fruits And Vegetables With Your Meals

Fresh fruits and vegetables have antioxidants that can prevent DNA damage and protect against cancers. 

A 2019 study analyzed the relationship between fruit and vegetable consumption and the risk of breast cancer in 182,145 women aged between 27 and 59. The study proves that women who consumed more cruciferous and yellow/orange vegetables and fruits had a lower risk of breast cancer. 

When you are occasionally eating smoked meat, include a large portion of fresh salad with the meal. The salad can make you partially full, prevent excessive meat consumption, and protect the body against cancers. 

Summary

  1. Smoking is a popular cooking technique that exposes meat to smoke and slow cooks it for several hours. Smoking, grilling, and barbecuing can all make meat carcinogenic and lead to all kinds of cancers, including breast cancer.
  2. When fat from the meat drips on the open fire that it is cooked on, it triggers flame and smoke. The smoke contains Polycyclic Aromatic Hydrocarbons (PAHs) that are carcinogenic. Smoked meat can increase breast cancer risk in women and increase mortality risk in existing breast cancer survivors.
  3. Changes in the CYP1A1 gene, CYP1B1 gene, and the SULT1A1 gene can increase the risk of developing breast cancer in women who consume a higher lifetime amount of smoked meat.
  4. Choosing alternative ways of cooking meat, trimming the fat portions before cooking, preventing the charring of meat, and including fresh fruits and vegetables with your smoked meat meal can all reduce breast cancer risk. 

References

What is Bevacizumab?

Bevacizumab is a medication used in the treatment of certain types of cancers. It is sold under the brand name Avastin. This medication is often used along with chemotherapy to prevent further growth of the tumor cells. 

Bevacizumab is known as an anti-vascular endothelial growth factor monoclonal antibody. Vascular Endothelial Growth Factor (VEGF) is a signaling protein that helps form blood vessels in the body. Blood supply is essential for cells to grow and multiply as it provides oxygen and nutrients. By acting as an anti-VEGF antibody, the medication starves the cancer cells and prevents their growth.

This is a biological medication (made from living organisms) approved by the US FDA (Food and Drug Administration). It is currently used as a first and second-line treatment option for colorectal cancers and as a first-line treatment option for non-small cell lung cancer.

Bevacizumab is also used to treat renal cell carcinoma, ovarian cancer, severe glioblastoma (tumor affecting the spine and brain), and advanced cervical cancer. 

Bevacizumab In Breast Cancer Treatment 

In 2008, the US FDA approved bevacizumab to treat metastatic (cancer that spreads from the primary location to other organs) HER2-negative breast cancer. In 2011 though, the FDA removed the medicine from the list of approved drugs for treating breast cancer.

According to the FDA, the potential side-effects and risks of this medication were much higher than its effect on breast cancer. They argued that bevacizumab only slightly increased the cancer-free period and did not increase the overall survival rate.

Though the medication has been removed from the approved drug list, doctors can still use it for breast cancer treatment with the patient’s approval.

How Does Bevacizumab Cause Hypertension?

There are many side effects of using Bevacizumab, and one such significant risk is bevacizumab-induced hypertension. Hypertension is consistently high blood pressure over 140/90. 

Three theories explain how bevacizumab usage can cause hypertension. 

Nitric Oxide (NO) Theory

NO is a molecule that is produced by almost all types of cells in the human body. NO helps the blood vessels relax and prevents high blood pressure. Studies show that reduced VEGF activity because of bevacizumab causes a decrease in the production of NO. Low NO levels lead to an increase in blood pressure. 

Many experts support this theory because, in most patients, the blood pressure normalizes once they stop receiving Bevacizumab. 

Kidney Impairment Theory

VEGF proteins are essential for the growth and maturation of the glomerular network in the kidneys. These are groups of small blood vessels located at the beginning of all the nephrons of the kidneys. The glomerular network filters the blood before it reaches the nephrons.

VEGF inhibition leads to abnormalities in the growth and maturation of the glomerular structure. This can lead to a condition called proteinuria. Proteinuria is the presence of excess proteins in urine. 

Certain studies report that people with proteinuria have a higher risk of developing hypertension.  

Pre-eclampsia-like Theory

Pre-eclampsia is a pregnancy complication that leads to high blood pressure. In pregnant women with pre-eclampsia, low VEGF levels are noted. As a result, this theory states that VEGF inhibition may be one reason for pre-eclampsia and, therefore, hypertension. 

A 2010 meta-analysis published in the American Journal of Hypertension analyzed the relationship between bevacizumab therapy and hypertension. The analysis looked at 20 studies and a total of 12,656 cancer patients. According to the study, people treated with bevacizumab had a higher risk of developing high blood pressure.


Another meta-analysis studied the relationship between bevacizumab and hypertension in 72 clinical trials involving 21,900 patients. According to the study, 25.3% of these patients developed hypertension, and 8.2% had grade 3 and grade 4 hypertension.

A different meta-analysis analyzed the prevalence of hypertension in 3155 non-small cell lung cancer patients. The study reported that 19.55% of people developed hypertension after being treated with bevacizumab, and 6.95% developed high-grade hypertension. 

How Does Genetics Influence Bevacizumab-induced Hypertension?

The SV2C Gene

The SV2C gene (Synaptic Vesicle Glycoprotein 2C gene) produces the SV2C protein. It plays a role in the normal functioning of the neural and endocrine cells and helps in low-frequency neurotransmission. 

rs2059157 is a Single Nucleotide Polymorphism or SNP in the SV2C gene. The T allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.

AlleleImplications
TIncreased risk of bevacizumab-induced hypertension
CNormal risk of bevacizumab-induced hypertension

rs10051982 is an SNP in the SV2C gene. The A allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.

AlleleImplications
AIncreased risk of bevacizumab-induced hypertension
GNormal risk of bevacizumab-induced hypertension

Non-genetic Factors Influencing Hypertension During Chemotherapy

Bevacizumab Dosage

The effect of bevacizumab is dose-dependent. People who were treated with a higher dose of the medication (>10 mg/kg) had a 7.5-times higher risk for developing hypertension. 

Age

People aged 60 and above have a higher risk of developing bevacizumab-induced hypertension when treated for cancer.

BMI Levels

People with BMI levels of 25 and above have a higher risk of developing bevacizumab-induced hypertension.

Pre Existing  Hypertension 

Those who have had high blood pressure before bevacizumab treatment are at a higher risk for developing high-grade bevacizumab-induced hypertension.

Type of Cancer

Among cancer patients who receive Bevacizumab, the risk of developing hypertension depends on the type of cancer. People with breast cancer or renal cell carcinoma show the highest risks for bevacizumab-induced hypertension.

Presence of other diseases

People with below pre-existing health conditions before bevacizumab treatment are at higher risk of developing hypertension during the treatment.

Tips To Prevent/Manage Hypertension Due To Chemotherapy (In Breast Cancer)

Talk To Your Doctor To Get The Right Information

If your doctor suggests bevacizumab medication along with chemotherapy, then talk to your doctor to understand the risks associated with the drug. Understand how effective it could be to treat your breast cancer and if the benefits outweigh the risks. 

Closely Monitor Your Blood Pressure Levels

The blood pressure starts rising from the first cycle of bevacizumab treatment. Make sure you closely monitor your levels at home and in a professional setup regularly. Talk to your doctor and opt for hypertension medications to prevent making the condition worse.

Manage Existing Hypertension Before Getting Treated For Breast Cancer

If you are already diagnosed with hypertension, make sure to stabilize your blood pressure levels  before starting cancer therapy. 

Start Antihypertensive Medications And Make Lifestyle Changes

Antihypertensive drugs help bring down blood pressure levels. It is recommended that you start on these along with your cancer treatment to prevent the risk of bevacizumab-induced hypertension. Make sure to consult a medical practitioner before getting started on any antihypertensives.

Some lifestyle changes can also help manage the condition.

Opt For Genetic Testing

Genetic testing before opting for bevacizumab will tell you how risky you are for developing hypertension during cancer treatment. If you are a high-risk patient, mention this to your doctor so they can monitor your blood pressure levels more frequently. 

Summary

  1. Bevacizumab is a medication used in the treatment of certain types of cancers. It is used along with chemotherapy to stop the growth of tumor cells.
  2. Though the FDA has currently removed bevacizumab from the list of approved medicines to treat breast cancer, doctors can still use it with the patient’s approval.
  3. Bevacizumab causes many side effects in cancer patients, including hypertension.
  4. Changes in some genes like the  SV2C gene can increase the risk of developing bevacizumab-induced hypertension.
  5. The risk of developing hypertension increases with higher doses of bevacizumab. People aged 60 and above and those with BMI levels about 25 are at higher risk too.
  6. The prevalence of other diseases like diabetes mellitus, high cholesterol, kidney problems, and peripheral artery disease also increases the risk of bevacizumab-induced hypertension.
  7. Antihypertensive medications can help bring down the risk of high-grade hypertension. People undergoing bevacizumab therapy should regularly monitor blood pressure levels. 

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References

The breast size of a woman keeps changing as she ages. At puberty, growth hormones and estrogen together cause breast development in girls. Breast size increases during pregnancy and breastfeeding. There is also a subtle increase in breast size during every menstrual cycle.

After menopause, the breasts go through atrophy. The term muscle atrophy refers to the loss of muscle tissue. Atrophy causes a reduction in breast size.

Breast Size And Breast Cancer Risk

Here are a few ways how breast size could contribute to breast cancer risk: 

Difficulty In Identifying Tumors

Bigger breasts make it difficult to identify lumps. Most women meet with a doctor when they self-examine the breasts and find a possible lump. Women who have larger breasts may not be able to identify the tumor before it gets big enough to push through the fat layers. 

Hence there can be a delay in diagnosis and treatment, increasing the risk of complications.

Big Breasts Are Associated With Obesity 

Bigger breasts are commonly noticed in obese and overweight women. Obesity is a very significant non-genetic factor that increases breast cancer risk.

Bigger Breasts In Women With Normal BMI Levels 

A study published in the International Journal of Cancer studied the relationship between breast size in premenopausal women and cancer risk.

The study assessed 89,268 premenopausal women in the age range of 29-47. They were followed up after 8 years. Out of these women, 803 had been diagnosed with breast cancer. The study recorded that women with BMI levels less than 25 and a bra cup size of more than D had a higher risk of developing breast cancer

Breast Size & Breast Cancer Risk: The Genetic Angle

The ZNF703 Gene

The ZNF703 gene contains instructions for the production of Zinc Finger Protein 703. This gene has been associated with the development of breast cancer. 

It behaves as a “classical oncogene” that regulates the growth and development of cells in breast cancer cell lines.

Oncogene is a mutated gene or gene containing errors that contribute to the development of cancer.

rs7816345

rs7816345 is a single nucleotide polymorphism or SNP in the ZNF703 gene. This SNP influences breast size and breast cancer risk.

The C allele of this SNP has been associated with bigger breast size and an increased risk for breast cancer. 

Non-Genetic Factors

Geographical Location 

According to some studies, breast cancer in women is less common in Asia than in Western countries. These studies report that this could be because the average breast size in Asian women is lesser than in Western countries, which brings down the risk. 

Increased Levels of Adipose Tissue 

Larger breasts have more adipose tissue. With more adipose tissue, the local estrogen levels increase. These local estrogen levels act as a slow-releasing source of carcinogens (cancer-causing agents). This increases the risk of developing breast cancer

Breast Parenchymal Patterns 

The breast parenchymal pattern is the proportion of glandular tissues to fatty tissues in the breasts. Glandular tissues in the breasts help make milk and include the lobes and ducts. A dense breast parenchyma pattern makes it difficult to identify tumors and hence causes diagnostic delays and complicates the cancer condition. 

Hormone Replacement Therapy (HRT)

HRT is used in treating the symptoms of menopause. HRT helps in balancing the levels of estrogen and progesterone in the body. 

According to a 2001 study, women who used HRT had increased breast density and hence had an increased risk of late diagnosis of breast cancer. Women who continued HRT for an extended period had consistently high breast densities throughout their life.

What You Could Do?

Genetic Testing

Genetic testing of BRCA genes can help you understand your risk for breast cancer. People with a family history of breast cancer or other risk factors should especially consider it.

Lose Weight

Obesity increases adipose tissues in the body, including in the breasts. This increases one’s risk of developing all kinds of cancer, including breast cancer. Losing weight can help bring down the risk considerably. Obese women with breast cancer have worse disease progression and lower overall survival rates. 

Breast Augmentation Surgery

Breast augmentation surgery is a process of changing the shape, size, and look of breasts. Some women use silicone implants to improve the look of breasts. In the United States, 2 million women have opted for implants in the past.

A study analyzed the impact of breast implants in 11,676 women between the years 1973 and 1986. Out of these, only 41 patients ended up with breast cancer. The expected number in the usual population was around 86. This study hence reports that breast augmentation surgery brings down the risk of breast cancer

Surgical Reduction Mammoplasty

This surgery is done to reduce the size of breasts. Here, breast tissues and excess skin from around the breasts are removed. Studies prove the number of breast cancer cases after surgical reduction mammoplasty was lesser than the expected numbers.

Summary

  1. Breast size is one of the risk factors for breast cancer - bigger size is associated with a higher risk for breast cancer.
  2. Increased difficulty in identifying lumps and increased estrogen production due to more adipose tissues in the breast can contribute to a higher risk of breast cancer.
  3. Genes that influence your breast size can also influence your breast cancer risk.
  4. Genetic testing of BRCA genes can help estimate breast cancer risk and be especially useful for women under the high-risk category.
  5. Maintaining a healthy weight helps restore estrogen balance and reduce breast cancer risk.  

References

According to the American Academy of Pediatrics(AAP), exclusive breastfeeding of infants for about the first six months and continued breastfeeding for a year or longer after introducing solid foods is recommended. 

The World Health Organization(WHO) also recommends exclusive breastfeeding for the first six months of an infant’s life

Exclusive breastfeeding refers to giving infants only breast milk and no other solid or liquid foods. According to the Centre for Disease Control and Prevention(CDC), only one in four infants are exclusively breastfed for the first six months

What Are The Benefits Of Breastfeeding?

Breastfeeding is beneficial for both the infant and the mother. Benefits of breastfeeding include:

Link Between Breastfeeding Duration & Breast Cancer

Research shows that mothers who breastfeed have a lower risk of developing pre and postmenopausal breast cancer. This benefit increases with an increase in the duration of breastfeeding for more than 6 months. 

Researchers have put forth several possible explanations to address the link between breastfeeding duration and breast cancer risk. All these explanations revolve around exposure to one of the female sex hormones, estrogen

Estrogen stimulates breast cell growth. Prolonged exposure to estrogen can increase the risk for breast cancer. Women have lower levels of estrogen during breastfeeding periods. This is because breastfeeding delays menstrual periods. The lifetime exposure to estrogen decreases with longer breastfeeding durations, and this decreases the risk of breast cancer.

Another reason is that the breast sheds a lot of tissue after lactation. During this process, it may also get rid of cells with damaged DNA that may lead to cancerous growth. Lactation may also lead to changes in the expression of genes found in breast cells. This can decrease the risk of cancer development.

A meta-analysis study showed that breastfeeding contributed to a 20% reduced risk for triple-negative breast cancer and a 10% reduced risk for estrogen receptor-negative breast cancer.

Breastfeeding Duration & Breast Cancer

Genetic Factors

Studies have estimated that the heritability of breastfeeding duration ranges from 44 to 54%. People with certain genetic types may tend to breastfeed their children for a longer duration than others. 

The XRCC2 Gene

The XRCC2 gene contains instructions for producing a DNA repair protein. This protein also helps maintain chromosomal stability. 

Changes in this gene are associated with increased risk of breast cancer and fanconi anemia. Fanconi anemia is a rare but serious blood disorder that prevents your bone marrow from making enough new blood cells for your body. It is passed down through families.  

rs3218536

rs3218536 is a single nucleotide polymorphism or SNP located in the DNA-repair gene XRCC2.

A 2010 study examined the role of DNA repair deficiencies in cancer development, especially in breast cancer. The study population was divided into women who breastfed and women who had never breastfed.

It was observed that among women who had never breastfed, those who carried the AG genotype of rs3218536 had a lower risk of breast cancer than those with the other genotypes.

After classifying this group according to the menopausal status, it was observed that postmenopausal women with the A allele had a lower risk of breast cancer than those with the G allele.

The MDM2 Gene

The MDM2 gene contains instructions for the production of Mouse double minute 2 homolog (MDM2) protein. It is also known as E3 ubiquitin-protein ligase Mdm2 protein. 

This protein acts as a negative regulator (suppresses the activity) of p53 tumor suppressor protein.

A study has reported that the activity of the MDM2 gene seems to be amplified in breast cancer cells. 

rs2279744

rs2279744, also known as 410T-G, has been studied for several years to determine its role in cancer. 

This SNP influences the ability of the MDM2 protein to bind to p53 tumor suppressor protein

The G allele of this SNP is associated with an increased risk for breast cancer, especially in women who have breastfed for less than 6 months and women who are obese. 

Non-Genetic Factors

Some factors that influence breast cancer duration include:

Recommendations For Breastfeeding

Increasing Breastfeeding Duration

Breast Cancer Screening

It is important to get periodic breast cancer screening done. Some screening options include mammography and breast MRI. You can check with your medical practitioner for suitable tests.

Video

Summary

  1. Breastfeeding has benefits to both the mother and the child. It provides all essential nutrients for the infant and lowers the risk of many health conditions, including breast cancer in the mother.
  2. Research shows that breastfeeding is linked to a reduction in the risk of breast and ovarian cancer. This is mainly due to the decreased exposure to estrogen during lactation. 
  3. Genetics influences both breastfeeding duration and breast cancer risk with shorter (<6 months) breastfeeding duration.
  4. Some factors that affect breastfeeding include postpartum depression, cracked or sore nipples, mastitis, latching issues, socioeconomic status, maternal employment, alcohol consumption, and smoking.
  5. Regular breast cancer screening with mammography or breast MRI can help with early diagnosis and support a good prognosis. 

References

What Is Breast Cancer Prognosis?

Breast cancer is the most common cancer in women in the developed and developing world. Breast cancer cases have a good prognosis if detected and treated early. 

Prognosis refers to the outlook or chance of recovery from a disease. It is an estimate of the likely course and outcome of a disease - breast cancer, in this case. This includes the likelihood of recurrence and life expectancy. 

Breast cancer prognosis is based on observing large groups of people affected by the condition over the years. It can be qualitative and described as excellent, good, or poor. It can also be quantitative in the form of survival rates or hazard ratios.

What Is Cancer Survival Rate?

The survival rate is determined by observing several people affected with breast cancer for many years, usually five or ten years. Survival rates are a key part of cancer prognosis. It indicates the percentage of people alive after a certain period of time, usually five years, after they were diagnosed. 

Survival rates can help give you a better understanding of how successful your treatment may be. Two main survival rates used in breast cancer cases include 

According to the National Cancer Institute, 90 percent of women with breast cancer survive five years after diagnosis, regardless of the stage. This indicates a 90% five-year survival rate - 90 out of 100 people diagnosed with breast cancer are likely to be alive after five years. 

What Is Hazard Ratio?

Another parameter used to determine prognosis in cancer patients is the hazard ratio. Hazard ratios are used to measure survival in a group of patients who have been given a specific treatment in a clinical trial setting. 

The patient group is compared with the control group, who are given a placebo, a treatment with no therapeutic value. 

Hazard ratio can either be equal to, lesser than, or greater than one. 

No difference in survival between the two groups receiving different treatment is denoted by a hazard ratio of 1. 

A value greater than or lesser than one indicates better survival in one of the treatment groups. 

Understanding Prognosis

Prognosis in terms of survival rates or hazard ratio is just an estimate based on previous outcomes of large groups of people with specific cancer. Every case is unique, and the survival rate is not a very accurate prediction of a specific person’s prognosis. 

The statistics can be confusing and alarming in some cases. Talk to your doctor about these statistics, how they apply in your case, and what you can do about it for better clarity. 

The prognosis for breast cancer survivors and their survival depends on many factors. This can be assessed only by a qualified physician familiar with the medical history, response to treatment, type and stage of cancer, and cancer-specific characteristics. 

How Genes Influence Breast Cancer Prognosis

A family history of breast cancer increases the individual’s risk of developing breast cancer. Genetics also influences breast cancer prognosis. Changes in certain genes may be responsible for the considerable differences in survival among breast cancer patients. 

The RAD51B Gene 

The RAD51B gene contains instructions for the production of a protein involved in DNA repair. Along with other proteins of this family, the RAD51B protein is involved in repairing damaged DNA. Changes in this gene can disrupt the DNA repair process and influence breast cancer prognosis. 

rs3784099 

rs3784099 is a single nucleotide polymorphism or SNP in the RAD51B gene. Carriers of the A allele are found to have lesser survival time and unfavorable prognosis.

Non-Genetic Factors

Apart from genetic factors, your doctor will consider several other factors to determine prognosis, including:

Recommendations to Improve Breast Cancer Prognosis

The statistics, survival rates, and hazard ratio values can be confusing. A doctor familiar with your medical history can help interpret breast cancer prognosis based on genetic and non-genetic factors. Certain ways to improve the prognosis of breast cancer include

Getting sufficient sleep: Breast cancer survivors need about 7 to 9 hours of sleep every night. In a study conducted by researchers from Fred Hutchinson Cancer Research Center, Seattle, women who slept for a period of 5 hours or less every night before being diagnosed with breast cancer had a 1.5 times higher likelihood of poor prognosis when compared with women who slept for 7 to 9 hours every night.

Regular exercise: Regular exercise improves prognosis; however, it might not be possible for everyone to exercise daily during the treatment. According to a study conducted by researchers at The University of California-San Diego Moores Cancer Center, a 12-week exercise program increased information processing speed by 2 times. This indicates cognitive benefits of exercise; however, the benefit is obtained only when the exercise program starts within 2 years of being diagnosed with breast cancer.

Alternate or Complementary Therapy: In North America, nearly 80% of breast cancer survivors depend on complementary therapy to cope with breast cancer. The most sought-after therapy is yoga. 

Yoga has been shown to reduce fatigue, improve sleep quality, physical functioning, and overall quality of life.

Lifestyle: Try to moderate or avoid smoking and alcohol consumption as these are risk factors for many types of cancer and may result in an unfavorable prognosis. Eat a healthy and balanced diet to maintain a healthy weight. 

Video

Summary 

  1. Breast cancer, the most common cancer in women in the developed and developing world, has a good prognosis if detected and treated early. 
  2. Prognosis is an estimate of the likely course and outcome of a disease. It can be understood as the outlook or chance of recovery from breast cancer. 
  3. Prognosis can be indicated using survival rates or hazard ratios. The 5-year survival rate of women with breast cancer is found to be 90%.
  4. Hazard ratios are used to measure survival in a group of patients who have been given a specific treatment in a clinical trial setting. The hazard ratio is denoted by a value equal to, less than, or greater than 1. 
  5. Certain changes in genes like the RAD51B are found to influence breast cancer prognosis. 
  6. Medical history, response to treatment, the type, stage, and grade of cancer, other specific characteristics of cancer, and menopausal status are the non-genetic factors that influence breast cancer prognosis. 
  7. Getting sufficient sleep, doing yoga, exercising regularly, and maintaining a healthy weight are some of the ways that can help improve breast cancer prognosis. 

References

Breast Cancer In Men

Breast cancer in men is a rare condition. Less than one percent of all breast cancer cases occur in men. According to the Centre for Disease Control, 1 in every 100 breast cancer cases in the United States occurs in men

Early diagnosis can lead to a better outcome for the disease. There is a lack of awareness about breast cancer in men, which leads to late diagnosis. Around 40% of breast cancer cases in men are diagnosed in the third or fourth stage

Breast cancer affects men and women differently. Men have a lesser and smaller amount of breast tissue compared to women. The cancerous lumps are smaller, but there is a higher chance of cancer spreading to other tissues in the body. 

What Are The Symptoms of Breast Cancer In Men?

Common symptoms of breast cancer in men include

How Does Genetics Influence Breast Cancer Risk In Men?

A family history of breast cancer increases the risk of developing breast cancer in men. About 1 in 5 breast cancer cases in men is hereditary.

The relative risk of breast cancer for a woman who has an affected brother is approximately 30% higher than for a woman with an affected sister.

Abnormal changes or mutations in certain genes result in an increased risk of breast cancer in men. BRCA1, BRCA2, CHEK2, PTEN, and PALB2 are few genes associated with breast cancer risk in men.

Men with a mutation in the _BRCA2_ gene have a 7 in 100 chance of developing breast cancer. 

Men with a mutation in the _BRCA1_ gene have a 1 in 100 chance of developing breast cancer. 

Non-Genetic Factors that Influence Breast Cancer in Men

Other than genetics, factors that influence breast cancer risk in men include:

Age

The risk of breast cancer increases with age. According to the CDC, the average age of men diagnosed with breast cancer is 65 years.

Estrogen Levels

Elevated levels of estrogen, one of the two main female sex hormones, contribute to the development of breast cancer. Certain conditions or treatments can lead to an increase in estrogen levels. These include:

Lifestyle Factors

Being overweight or obese and engaging in low levels of physical activity contribute to the risk of breast cancer. Heavy drinking may also increase breast cancer risk

Radiation

Men who have undergone radiation treatment to the chest area may be at higher risk of developing breast cancer. 

Testicular Conditions

Injury or swelling in the testicles, an undescended testicle, or surgery can increase the risk of breast cancer.

Recommendations To Lower Breast Cancer Risk In Men

Early Detection

Early detection of breast cancer means early treatment and a better outlook. This helps prevent the spread of breast cancer to other tissues in the body. Males with a family history of breast cancer should undergo regular screening. 

Males at high risk of developing breast cancer can opt for genetic testing to see if they carry pathogenic variants. A healthcare provider and a genetic counselor can help you understand risk assessment and the implications of the test. They can tell you about the pros and cons of the test, your testing options, and further interpret the results and their significance. 

Controlling Estrogen Levels

There are several health conditions like hypogonadism that can increase estrogen levels. Even certain antibiotics can increase estrogen levels. It is important to consult your doctor for advice regarding lowering your estrogen levels in these cases. 

Lifestyle

Staying active, eating healthy, quitting smoking, and cutting down on alcohol can help keep your hormones in check and lower the risk of breast cancer. 

Treatment

Treatment options include chemotherapy, radiation, hormone therapy, targeted therapy, and surgery. Based on the diagnosis, the doctor will prescribe the necessary treatment. 

Video

Summary 

  1. Lesser than 1% of all breast cancer cases are found to occur in men. Due to a lack of awareness, breast cancer in men is usually diagnosed in the later stages.
  2. Men with a family history of breast cancer are more likely to develop the disease. 
  3. Certain changes or mutations in some genes, including BRCA1, BRCA2, CHEK2, PTEN, and PALB2, contribute to the development of breast cancer in men.
  4. Old age, elevated estrogen levels, certain lifestyle factors, prior exposure of the chest area to radiation treatment, and testicular conditions are some non-genetic factors that influence the risk of breast cancer in men. 
  5. Early detection can lead to a better outlook and prevent cancer from spreading. Staying active and reducing alcohol consumption are some of the lifestyle changes that can help.
  6. Genetic testing is a good option for males with a family history of breast cancer. A trained healthcare professional or genetic counselor can outline the steps and help you interpret the results.

References

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