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.
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.
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.
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.
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.
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.
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.
Maintaining a healthy weight can help reduce estradiol fluctuation in the body and decrease the risk of breast cancer.
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.
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.
Some genes promote higher growth of estrogen receptors during menopausal hormone therapy. This increases the risk of ER-positive breast cancer.
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 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.
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.
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 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.
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 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 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.
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.
Chemotherapy is one of the many options available to treat cancer. Chemotherapy involves using drugs to stop cancer cells in the body from growing, multiplying, dividing, and spreading. Chemotherapeutic drugs are of different types, and not all of them work in the same way.
While chemotherapy affects the cancer cells, the drugs used in the treatment cannot differentiate between normal and cancerous cells, which results in some damage to healthy cells and tissues.
The most common example of this is the loss of hair in people undergoing chemotherapy treatment.
Around 10% of patients undergoing chemotherapy for breast cancer experience severe chemotherapy-induced alopecia.
Though chemotherapy is one of the primary treatment options for cancer, other newer treatments may be preferred for certain types of cancer.
Chemotherapy is used as one of the main treatments for breast cancer cases, during which drugs are used to target and destroy breast cancer cells.
The drugs may be administered orally (by mouth) or intravenously (injected directly into the veins).
In most breast cancer cases, chemotherapy is used alongside surgery, radiation, and hormone therapy.
Chemotherapy improves breast cancer treatment outcomes and allows the individual to live longer and enjoy a better quality of life.
However, chemotherapy administered for breast cancer can have side effects, which may be mild and temporary.
In breast cancer cases, chemotherapy may be given in the following scenarios:
Chemotherapy may be given before breast cancer surgery to reduce the tumor’s size and make it easy to remove with a less extensive surgical procedure. This procedure is called neoadjuvant therapy and is used to remove large breast tumors.
In some cases, chemotherapy is given after a surgical procedure has been done to remove the tumor. This is called adjuvant chemotherapy, and it is shown to reduce any remaining cancer cells that may have been left behind after the surgery. Chemotherapy given after a breast cancer removal surgery reduces the chances of recurrence.
Chemotherapy is the primary treatment of choice in advanced breast cancer cases where cancer has spread outside the breast to the underarm area.
Common Drugs Used in Adjuvant and Neoadjuvant Therapies include:
Chemotherapy drugs used in the treatment of advanced breast cancer include:
Early breast cancer cases are usually treated with a combination of chemotherapeutic drugs, but advanced cases of the disease are mostly treated with single drugs.
If breast cancer has been diagnosed as HER-positive (Hormone Receptor-Positive), chemotherapy drugs may be supplemented with one or more drugs targeting the HER-2 receptors.
Chemotherapy for any type of cancer, including breast cancer, can have side effects. Some common side-effects of chemotherapy include:
Hair loss, also called alopecia, is very common during breast cancer chemotherapy. This happens because the chemotherapy drugs target rapidly dividing cells– both healthy and cancerous cells.
Hair follicles are one of the many rapidly dividing cells in the body found in the skin. When chemotherapy drugs are looking to destroy any rapidly dividing cells, they also destroy hair follicles. This results in hair thinning and loss after a few days of chemotherapy. Hair loss usually happens very quickly following just a few chemotherapy sessions.
Analyzing genetic risk factors can help develop an effective way to reduce chemotherapy-induced alopecia in breast cancer patients.
ATP-binding Cassette Subfamily B Member 1 is a part of the ATP-Binding Cassette family of genes. These genes make proteins (called ABC proteins) that help transport various molecules across cell membranes in multiple tissues.
These ABC proteins also help decrease the accumulation of xenobiotic compounds (compounds not produced by the body and are found in the body) like drugs in the case of multidrug-resistant.
rs1202179 is a Single Nucleotide Polymorphism, or SNP found in the ABCB1 gene located on chromosome 7.
The C allele of this SNP has been linked to a decrease in the expression of the ABCB1 and subsequent increased risk of chemotherapy-induced alopecia (pCIA) in women being treated for breast cancer.
This effect is due to the accumulation of transporting drugs like docetaxel, resulting from P-glycoprotein deficiency. P-glycoprotein is a protein produced by the ABCB1 gene to eliminate the drug.
Deficient P-glycoprotein causes an increased exposure of hair follicles to docetaxel damage, resulting in hair fall.
Protocadherin-related 15 or PCDH15 is a gene that gives instructions for the production of membrane proteins.
These membrane proteins are responsible for retinal and cochlear functions and maintaining calcium-dependent adhesion between cells in the body.
The presence of the G allele in SNP rs7919725 in the PCDH15 gene increases the risk for drug-induced grade 2 alopecia.
Transmembrane Protein 132C or TMEM132 C is located on chromosome 12. It plays a role in cell adhesion, i.e., how cells attach to their neighboring cells.
rs11059635 is an SNP in the TMEM132C gene. The G allele of this SNP plays a role in chemotherapy-induced alopecia due to its response to Paclitaxel.
Calcium voltage-gated channel auxiliary subunit beta 4 or CACNB4 is a gene that provides instructions for making calcium channels.
Calcium channels are essential for transporting calcium ions inside the cells. They enable cells to generate and transmit electrical impulses for muscle contractions, cell-to-cell communication, and regulate genes.
Therefore, any abnormal changes in the CACNB4 gene can cause neurological and muscular conditions.
rs3820706 is an SNP in the CACNB4 gene and is located on chromosome 2.
The G allele of SNP rs3820706 plays a role in chemotherapy-induced alopecia.
Non-genetic factors that influence hair loss during breast cancer chemotherapy include:
Hair loss during chemotherapy is dreaded by many women undergoing treatment for breast cancer. Many methods have been studied that can prevent hair loss due to breast cancer chemotherapy. These include:
In this method, ice packs or an ice cap are placed on the scalp during a chemotherapy session. These help contract the blood vessels in your scalp to prevent the chemotherapy drugs from reaching your hair follicles.
Some studies have shown that this prevention method is applicable only with certain chemotherapeutic drugs like taxanes. A study published in 2017 in the Journal of the American Medical Association stated that using scalp cooling in women with stage I and II breast cancer resulted in less than 50% hair loss after the fourth chemotherapy session.
Scalp cooling or using ice caps has its side effects, such as discomfort or headaches due to the cold.
Another method to prevent hair loss during breast cancer chemotherapy is scalp compression. This method may be used with or without scalp cooling. Clinical trials are still underway to determine the effectiveness of scalp compression on hair loss prevention but what is known so far is that this method is less effective than scalp cooling.
Medications are often recommended to manage hair loss caused due to breast cancer chemotherapy. These medications do not prevent hair loss but help in faster regrowth. Common medications that help hair regrowth include topical application of 2% Rogaine (minoxidil) and Panicum miliaceum.
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.
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.
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.
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.
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 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.
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.
|T||Increased risk of bevacizumab-induced hypertension|
|C||Normal 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.
|A||Increased risk of bevacizumab-induced hypertension|
|G||Normal risk of bevacizumab-induced hypertension|
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.
People aged 60 and above have a higher risk of developing bevacizumab-induced hypertension when treated for cancer.
People with BMI levels of 25 and above have a higher risk of developing bevacizumab-induced hypertension.
Those who have had high blood pressure before bevacizumab treatment are at a higher risk for developing high-grade bevacizumab-induced hypertension.
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.
People with below pre-existing health conditions before bevacizumab treatment are at higher risk of developing hypertension during the treatment.
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.
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.
If you are already diagnosed with hypertension, make sure to stabilize your blood pressure levels before starting cancer therapy.
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.
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.
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.
Breastfeeding is beneficial for both the infant and the mother. Benefits of breastfeeding include:
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.
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 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 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 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, 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.
Some factors that influence breast cancer duration include:
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.
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.
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.
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.
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.
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 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 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.
Apart from genetic factors, your doctor will consider several other factors to determine prognosis, including:
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.
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.
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.
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.
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 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.
- 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.
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.
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.
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.
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.
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.
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 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 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.
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
Physically active women who have a healthy weight and lead a healthy lifestyle have a reduced risk of developing ER-negative breast cancer.
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 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.
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.