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.
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.
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.
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.
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.
Breast cancer is one of the most common types of cancer affecting women. According to the World Health Organization (WHO), 2.3 million women were diagnosed with breast cancer, and 685,000 lost their lives globally in 2020.
As of 2020, 7.8 million women have been diagnosed with breast cancer and are alive in the last five years.
Breast cancer survivors are at risk for different health conditions - fatigue, mental health issues, and breast cancer recurrence - to name a few. They must also be aware of the higher risk they carry for developing a second non-breast cancer.
People who have had breast cancer in the past are at higher risk for developing other types of cancers, including:
A 2006 study collected data from 13 different cancer registries in places like Singapore, Canada, Australia, and Europe. The study analyzed the data of 525,527 women and followed them for 10+ years.
According to the study, when compared to women who did not have a history of breast cancer, women with past or present breast cancer had:
Another study analyzed the risk of Secondary Non Breast Cancers (SNBCs) in 58,068 Dutch women diagnosed with breast cancer between 1989 and 2003. According to the study, women who had breast cancer in the past had a small but significant risk for developing esophageal cancer, stomach cancer, colon cancer, rectum cancer, uterus cancer, ovarian cancer, soft tissue sarcoma, acute myeloid leukemia (AML), and non-Hodgkin’s lymphoma.
The BRCA1 gene (BRCA1, DNA repair associated gene) produces a tumor suppressor protein. This protein is considered beneficial as it hinders uncontrolled cell division, thereby lowering cancer risk.
Abnormal changes (or variations) in this gene can lead to low or no production of the tumor suppressor protein and increase one’s risk for developing cancers.
A study reported that BRCA1 variations lead to breast and ovarian cancers and also increase the risk of other cancers like colon cancer (11.1%), pancreatic cancer (3.6%), and gastric cancer (5.5%).
The BRIP1 gene (BRCA1 interacting protein C-terminal helicase 1) contains instructions for producing a protein that repairs double-strand breaks in DNA.
Abnormal changes in this gene result in lower production of this protein, which increases the risk of many types of cancers. Cancers associated with variations in this gene are:
The PALB2 gene (Partner And Localizer Of BRCA2 gene) contains instructions for producing a protein that works with the BRCA2 protein to repair damaged DNA and suppress tumor growth. Abnormal changes in this gene affect the ability of the BRCA2 gene to prevent tumor cell formation.
Apart from breast cancer, this gene is associated with the risk for:
The CHEK2 gene (Checkpoint kinase 2) is also a tumor suppressor gene and produces a kinase enzyme protein called CHK2.
Abnormal changes in this gene increase the risk of developing breast cancer by two times. It also increases the risk of:
The PTEN gene produces an enzyme that acts as a tumor suppressor. Almost all tissues in the body have this enzyme in specific quantities. This enzyme prevents the abnormal division of cells by encouraging self-destruction (a process called apoptosis) of these cells. In people with past or present breast cancer diagnoses, variations in this gene can result in an increased risk of:
One of the main non-genetic factors that increase a person’s risk of developing other cancers is radiation exposure.
There are three basic radiotherapy treatment solutions for breast cancer.
1. Three-dimensional Conformal Radiotherapy (3D-CRT)
2. Intensity-Modulated Radiotherapy (IMRT)
3. Volumetric Modulated Arc Therapy (VMAT)
Many studies report a higher risk of second cancer because of radiation exposure.
A large study analyzed the risk of second cancers in 46,176 breast cancer survivors. According to the study, one out of 200 women who had received radiation therapy for breast cancer had a higher risk of being diagnosed with other cancers.
Chemotherapy is a treatment that uses various drugs to kill abnormally growing tumor cells in the body. It is the most common treatment option for cancer.
Some types of chemo drugs given during breast cancer treatment are associated with an increased risk for developing other types of cancers.
Chemo agents that are linked with second cancer risks are:
Patients who go through chemotherapy for a longer time or get treated with higher doses of drugs are at a higher risk of developing other cancers.
While patients who had exposure to radiation therapy and chemotherapy were at higher risk for developing second non-breast cancers, people under the age of 40 who received these treatments were at more risk than the elderly who received treatment.
Smoking increases the risk of breast cancer and all other cancers. Smokers diagnosed with breast cancer are at higher risk for developing other cancers in the future when compared to non-smokers.
A 1994 study tried to find the relationship between smoking, breast cancer, radiation therapy, and the risk of second cancers. According to the study, radiation therapy for breast cancer increased the risk of developing other cancers in smokers and non-smokers. However, in smokers, this risk was much higher.
Genetic testing can be a good aid for treatment planning and risk management if:
Genetic testing will look for specific genes that can increase your risk for breast and other cancers. It will tell you if you are at higher risk for second cancer. In case you belong to the high-risk category, regular screening can help you.
Talk to your doctor about the dosage and type of chemotherapy and radiation treatment you will be receiving for your breast cancer. Some treatments may increase your risk for breast cancer than others.
Some lifestyle changes can lower your risk of developing cancer.
The fear of breast cancer recurrence and the fear of developing second cancers can lead to high stress. Stress causes abnormal changes in the cells and can be a cause for cancer recurrence. Fear and stress lead to unwanted behaviors like alcohol abuse, smoking, and excessive eating. All these also increase the risk of developing other cancers. Practicing mindfulness and talking to a mental health expert might help you in controlling stress.
Radiation is the transmission of energy through space or a medium. The transmission is in the form of waves or particles. Some radiation is naturally created, while others are artificially made.
There are two types of radiation depending on how they affect other atoms and molecules.
Non-ionizing radiation: This is the type of radiation that human beings are regularly exposed to. The radiation is not strong enough to affect atoms and molecules in the body.
Types of non-ionizing radiation
Ionizing radiation - This radiation is strong enough to ionize atoms and molecules. Ionization is the process of removing an electron from an atom and making it positively charged. Ionization causes electron/proton imbalance in the atoms, and this affects the cells in the body.
|Types of ionizing radiation|
|Alpha radiation||It consists of two protons and two neutrons. It cannot penetrate past the outer skin and causes no damage|
|Beta Radiation||It consists of fast-moving electrons. It can penetrate the outer skin and is used to treat superficial tumors.|
|Gamma Radiation||It consists of protons that have neither electric charge nor mass. As a result, the radiation penetrates through the skin and leads to cell damage.|
|X-rays||X-rays are man-made electromagnetic radiation. X-rays are similar to gamma rays and can penetrate the human body.|
|Neutron radiation||It consists of free neutrons produced in large numbers due to nuclear fission or fusion reactions.|
There are two categories of ionizing radiation sources - natural and artificial.
Natural Sources Of Ionizing Radiation
According to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), there are four natural sources of ionizing radiation.
Artificial Sources Of Ionizing Radiation
Radiation exposure can cause breast cancer in different ways.
Researchers studied the effect of radiation exposure on Japanese women who survived the atomic bombing of 1945. The study identified 807 first-time breast cancer cases and 20 second-time breast cancer cases in the survivors. The study reported the following:
Mammography is a diagnostic procedure that uses X-rays to check for breast cancers. In a diagnostic mammogram, a minimum of two X-ray films of the breasts is taken at two different angles. On average, the dose of radiation for these two pictures is 0.42 mSv (millisieverts). Dosage is the amount of ionization that occurs due to radiation exposure.
According to the National Breast Cancer Foundation, women over 40 years are advised to get their annual mammographic screening done. In addition, doctors may recommend more frequent screening in the following cases.
According to a study, women with large, dense breasts who undergo repeated mammography may be at higher risk for radiation-induced breast cancer and breast cancer death.
The researchers projected that "annual digital mammographic screening of 100,000 women (aged 40 to 74) would induce 125 cases (~0.1%) of breast cancer, and that there would be 16 deaths (0.016%)."
However, this number appears to be almost negligent when compared to the 968 breast cancer deaths (9.7%) that would have been averted by early detection from screening.
The H19 gene helps produce a molecule called the non-coding RNA. The non-coding RNA is considered to be a tumor suppressor and is protective against different kinds of cancers. Certain changes in this gene can encourage the growth and multiplication of radiation-damaged cells. This can lead to tumors.
rs2107425 is a single nucleotide polymorphism or SNP in the H19 gene. A particular study reports that people with the A allele of this SNP, are at a higher risk for developing breast cancer when exposed to high doses of radiation.
The ERCC2 gene helps make a protein called XPD (Xeroderma Pigmentosum complementation group D). It plays a role in repairing damaged DNA.
rs13181 is an SNP in the ERCC2 gene. In people with the wild AA genotype of this SNP, there is an association between occupational radiation exposure and breast cancer.
However, this association is not seen in the AC and CC genotypes.
|AA||Association between occupational radiation exposure and breast cancer|
|AC||No association between occupational radiation exposure and breast cancer|
|CC||No association between occupational radiation exposure and breast cancer|
Studies show that women under 20 are at the highest risk for developing breast cancer due to radiation exposure. According to these studies, women above 50 years have minimal or no recorded risk for radiation-induced breast cancer.
Few women may have undergone radiation therapy in the past, increasing the risk of breast cancer. Some women who are in the high-risk category include:
The periods of pregnancy bring down the risk of radiation-induced breast cancer. Women who have an early full-term pregnancy are more protected against breast cancer.
According to some studies, during pregnancy and breastfeeding, the number of weak breast cells affected by radiation is lesser, bringing down breast cancer risk.
Family history affects the relationship between radiation exposure and breast cancer. The Family history affects the relationship between radiation exposure and breast cancer. The BRCA1 and BRCA2 gene changes lead to inherited breast cancer.
Women with changes in these genes are already at a higher risk of developing breast cancer. Radiation exposure can increase the risk.
According to the American Cancer Society, women between the ages of 40 and 44 can start screening for breast cancer but don’t have to get mammograms unless their doctors instruct. Women between 45 and 54 need to get one mammogram a year. Women older than 55 should get two mammograms done a year.
If you are younger than 40, talk to your doctor and only get a mammogram if necessary. While mammogram screening helps identify tumors early and treat breast cancer early, getting unnecessary mammograms may trigger breast cancer in a few.
Occupational radiation exposure happens in workplaces when the person handles radioactive sources or works with equipment generating radiation.
Lifestyle habits like smoking and drinking, excessive weight gain, the types of food you choose, and exposure to other environmental carcinogens can all lead to breast cancer.
Unhealthy lifestyle choices, along with radiation exposure, increases breast cancer risk drastically.
Genetic testing will help identify how harmful radiation exposure is for your breast cells. You can also know if you are at risk for developing inherited breast cancer because of the abnormal functioning of the BRCA1 and BRCA2 genes.
Excess body weight is responsible for about 11% of cancers in women and 5% of men. Did you know that the risk for postmenopausal breast cancer is 1.5 times higher in overweight women and 2 times higher in women with obesity? Let’s understand more about how obesity contributes to breast cancer risk.
Being overweight or obese increases the risk for breast cancer, especially in postmenopausal women. Your Body Mass Index (BMI) determines if you have a healthy weight, are overweight, or are obese.
A BMI between 18 and 24.9 is considered healthy. A BMI between 25 and 29.9 means that you are overweight. If your BMI is higher than 30, it could indicate obesity.
Women with a BMI over 25 are at an increased risk of developing breast cancer than those with a healthy weight. In addition, this risk is exceptionally high after menopause. Being overweight or obese also increases the risk of breast cancer recurrence.
The exact link between increased weight and breast cancer risk is complicated and multifactorial. The high risk appears to be connected to the estrogen production by the fat cells.
In premenopausal women, estrogen is mainly produced by the ovaries. However, in postmenopausal women, adipose tissues or fat tissues is the main source of estrogen production.
The number of fat cells is higher in overweight or obese women. This results in increased estrogen production, which is a risk factor for breast cancer development. This is especially of significance for Hormone-Receptive breast cancers that develop and grow on exposure to estrogen.
It has been found that women who are obese after menopause are at a 30% higher risk of developing breast cancer. Gaining more than 22 pounds after menopause can increase the risk of breast cancer by 18%.
Studies report an association between obesity and a lower risk of Estrogen-Receptor Positive (ER-Positive) breast cancer but a higher risk of ER-negative and Triple-negative breast cancer in premenopausal obese women.
In addition, a study from the Breast Cancer Surveillance Consortium database showed that obesity is associated with an increased risk for Inflammatory Breast Cancer (IBC) in premenopausal women.
The Million Women Study followed 1.2 million UK women ages 50 to 64 years for a mean of 5.4 years. Out of these, 45,037 women had breast cancer. The study identified a nearly 30% higher risk of developing postmenopausal breast cancer with obesity.
A meta-analysis of 34 studies reported that the risk of postmenopausal breast cancer increases with every 5kg/m2 increase in BMI.
Obesity affects the prognosis and survival rate of breast cancer patients. A recent study found that obese women with breast cancer experienced an 11% decrease in overall survival rate, irrespective of their menopausal status.
Besides breast cancer, obesity is a risk factor for type 2 diabetes and heart diseases - the latter seems to be the leading cause of mortality in women with early-stage breast cancer.
It has also been observed that obese women with breast cancer are more likely to experience complications during surgery and radiation.
In addition, systemic chemotherapy and endocrine therapy for treating breast cancer are less effective in obese women, further reducing prognosis and survival rate.
The mortality rate in obese women is also dependent upon the type and characteristics of the tumor. For example, obese women with Luminal A and Luminal B breast cancer were 1.8 and 2.2 times more likely to die from cancer than normal-weight women.
However, obesity was not associated with breast cancer-specific mortality among women with HER2- and triple-negative tumors.
rs16945628 is a Single Nucleotide Polymorphism (SNP) in the BRIP1 gene. The TT genotype of this SNP is associated with an increased risk of breast cancer in women with a BMI of ≧25 kg/m2.
Insulin-like Growth Factor Binding Protein 3 or IGFBP3 gene is located on chromosome 7 and participates in cell growth, multiplication, and differentiation, and cancer development in the breast tissue.
rs2854744 is an SNP in the IGFBP3 gene linked to the risk of breast cancer. The CC genotype of this gene significantly increases the risk of breast cancer compared to the AA genotype. This increase was found to be more pronounced in older women.
Studies also showed that women carrying the AC+CC genotypes of the IGFBP3 gene had a larger tumor size in the breast.
Obesity is a critical non-genetic risk factor for breast cancer.
According to a 2019 study, sustained weight loss is associated with lower breast cancer risk for women aged 50 years and older.
The researchers looked at 180,885 women from 10 studies. The women's weights were recorded 3 times over a period of 10 years; once when they enrolled and once every 5 years.
Weight changes of 2 kilograms or less (about 4.4 lbs) were counted as stable.
The study reported the following*:
*Compared with those whose weight was stable.
The study did not include women on postmenopausal hormone therapy, and the results were more prominent in obese or overweight women.
Despite this, the study suggests that even a modest amount of sustained weight loss can lower your breast cancer risk and improve survival rate, if diagnosed with breast cancer.
Triple-negative breast cancer (TNBC) is one of the aggressive subtypes of breast cancer that occurs in women. Unfortunately, the prognosis and management of TNBC pose great difficulty. However, a new study by the University of Texas M. D. Anderson Cancer Center reports an association between statin use and improved survival rates among TNBC affected individuals.
TNBC is a subtype of breast cancer that lacks any receptors generally found in breast cancer cells. The other types of breast cancers have receptors for any of these hormones:
*Note: Receptors are proteins that receive chemical signals by binding to specific molecules.
TNBC represents about 10-15 % of all breast cancers.
The presence of even one of the receptors makes treating breast cancer easier. Doctors can then treat cancer by targeting these receptors to get inside the cancerous cell and destroy it.
However, in TNBC, the lack of receptors limits the treatment options.
According to the American Cancer Society, based on diagnosis information between 2010-2016, the 5-year survival rate for TNBC affected individuals is 77%. However, these statistics are subject to variation depending on the cancer progression stage and grade of the tumor.
Know about your BRCA status and risk for breast cancer using Xcode Life’s BRCA and Breast Cancer Report.
Statins represent a class of drugs usually prescribed for heart attacks and stroke. Statins help in lowering blood cholesterol levels.
Statins can be broadly classified into lipophilic and hydrophilic statins. Lipophilic statins are fat-soluble, and hydrophilic are water-soluble.
Notably, lipophilic statins quickly enter the cells and communicate with cell membranes. In contrast, hydrophilic statins show more selectivity to liver cells.
Explore your body’s response to different types of statins with Xcode Life’s Personalized Medicine report.
The earliest research to report a link between statin and TNBC was a study in 2013. According to the study, statins activate the inhibition of TNBC through the PI3K pathway. They also suggested Simvastatin as a potent candidate for the treatment of TNBC, especially for wild-type (a form of the gene occurring naturally and predominating a population) expression of PTEN in the TNBC tumors.
Another study, done in 2017, to investigate the outcome of statin use on TNBC produced mixed results. The study observed no apparent association between statin use and overall survival (OS) in an unselected cohort of TNBC patients.
However, statin use significantly improved OS within a specific group of test subjects whose cholesterol and triglyceride levels were controlled. In addition, statin use showed a pronounced effect on survival rate even for another group of triple-negative patients who experienced metastatic failure.
*Note: 1. Overall survival: Length of time from the diagnosis date or start of treatment that a patient is still alive.
2. Metastasis: Stage of cancer where the cancerous cells start migrating from their origin site and infect other healthy parts of the body.
In 2019, a study found that the effect of statin use on breast cancer survival depended on the duration of statin use. In the test subject group, patients who had a medical history of statin use for more than five years experienced a conspicuous improvement in survival rate.
(NB: The findings of the study were irrespective of breast cancer type or receptor subtype)
In 2020, a statistical study on the clinical outcome of statin use on breast cancer diagnosis involving multiple research studies found a significant association between statin use and decreased recurrence rate and breast-cancer mortality in women.
|2013||Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway.||Statin activates inhibition of TNBC through the PI3K pathway|
|2017||Impact of Statin Use on Outcomes in Triple Negative Breast Cancer.||Statin use improved survival rates in TNBC patients who:Had their cholesterol and triglyceride levels controlledExperienced metastatic failure|
|2019||Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer.||Long-term (>5 years) use of statin improved survival rates in TNBC patients|
|2020||Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies.||Significant link between statin use and decrease in the recurrence rate of TNBC and disease-specific mortality in women.|
A study led by Kevin Nead of the University of Texas M. D. Anderson Cancer Center explored the outcomes of statin use in breast cancer patients. This study was the first to investigate the effect of statin use on all subtypes of cancer, focusing mainly on TNBC.
According to Nead, “Previous research has looked at breast cancer as only one disease, but we know there are many subtypes of breast cancer, and we wanted to focus our research on this particularly aggressive form of breast cancer that has limited effective treatment options.”
The study analyzed 23,192 female patient data included in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry and the Texas Cancer Registry (TCR)-Medicare databases between 2008-2015. Patients were at least 66 years of age and diagnosed with stage I-III breast cancer.
2281 patients out of 23,192 were individuals who commenced statin use within 12 months of a breast cancer diagnosis. Out of these 2281 patients, 78.1% were white, 8.9% were black, 8.4% were Hispanic, and 4.5% belonged to other races.
The study also assessed the type-specific effect of statin on breast cancer outcomes.
Many genetic and environmental factors can increase or decrease a person’s risk of developing breast cancer.
One such factor is the amount of fat you consume.
The fat you consume is usually stored as a reserve in the adipose tissue and used as an energy source when you consume fewer calories than what the body needs.
Fats play a role in protecting your internal organs, keeping you warm, and controlling the action of different hormones.
High levels of dietary fat may increase the sex hormones in a woman’s body (estrogen and progesterone). Some researchers assume that this may be why fats increase the risk of breast cancer, especially hormone-receptor-positive breast cancers.
High dietary fat intake also increases the risk of obesity. Obesity, in turn, increases postmenopausal ER-positive breast cancer risk by increasing estrogen production in the body.
A 2003 study assessed the risk of breast cancer in 90,655 premenopausal women between the ages of 26 and 46. This 8-year study identified 714 cases of breast cancer during the follow-up.
According to the study, women who had consumed high animal dietary fats had a slightly increased risk for breast cancer. The study identified that red meat, animal fat, and dairy products specifically increased cancer risk.
Does The Type of Fat Matter?
There are four major types of dietary fatty acids.
Saturated and trans fat are considered unhealthy fats as they increase blood cholesterol levels and lead to heart conditions.
Unsaturated fats are healthy as they bring down cholesterol levels and also boost heart health.
When it comes to breast cancer risk, the type of fat you consume definitely matters. Many studies relate saturated fats and trans fats to an increased risk for breast cancer. Conversely, some unsaturated fats seem to be protective against breast cancer.
A 2003 meta analysis studies the risk of breast cancer in people who consumed excess dietary fats.
According to the meta-analysis, short-term and long-term studies found that people who consumed excessive saturated fats and meat had a 13% higher risk of breast cancer.
Another combined analysis study that included data from 12 case-controlled studies found a positive relationship between saturated fat intake and breast cancer.
This study also reports that with changes in the diet, up to 24% of postmenopausal women and 16% of premenopausal women in North America decreased their risk of developing breast cancer.
Industrial Trans Fatty Acids (ITFAs) are trans fats produced in industries and added to various dairy products, snacks, and pastries. Ruminant Trans Fatty Acids (RTFAs) are made in the bodies of cows, goats, sheep, and other animals as a result of bacterial action. RTFAs are present in most animal fats, and consuming these fats increase RTFA levels in the body.
The European Prospective Investigation into Cancer and Nutrition (EPIC) found a positive relationship between ITFA and RTFA consumption and the risk of breast cancer in 318,607 women.
A 2005 study analyzed the effects of unsaturated fatty acids on breast cancer risk. The study reported that omega-3 fatty acids, a type of polyunsaturated fatty acid, brought down the risk of breast cancer.
In contrast, omega-6 fatty acids, a different kind of polyunsaturated fatty acid, increased the risk of breast cancer.
A 2015 article observed the interaction of omega-3 fatty acids and omega-6 fatty acids in the development of breast cancer in 1463 breast cancer patients and 1500 controls. The study suggests that American women can reduce their risk of breast cancer by increasing their omega-3 fatty acid intake (omega-3 has anti-inflammatory properties) and decreasing the consumption of omega-6 fatty acids (Omega-6 induces inflammation).
When it comes to MUFAs, the type of food plays a role in increasing or decreasing cancer risk.
A 1993 meta-analysis study reported that MUFAs also increase a woman’s risk of developing breast cancer.
Another study reported that oleic acid and palmitic acid, types of monounsaturated fatty acids, increased the risk of breast cancer in women.
Olive oil, which is rich in MUFA, seems to protect against cancers, though. People who chose olive oil over other lipids like butter had high levels of protection against all cancers, including breast cancer.
The DOCK1 gene (Dedicator of cytokinesis gene) helps create the DOCK180 protein that plays a role in signaling between cells.
rs113847670 is a single nucleotide polymorphism or SNP in the DOCK1 gene. It is associated with breast cancer risk. The T allele of this SNP results in 5 times higher risk of developing breast cancer on excess intake of saturated fats.
|T||5-times higher risk of developing breast cancer on excess intake of saturated fats|
|C||Normal risk of breast cancer on excess intake of saturated fats|
Obesity is one of the factors that can contribute to increased breast cancer risk. Excess intake of fats can lead to weight gain and obesity too. As a result, the combination of obesity and excess fat intake can aggravate breast cancer risk.
This is true, especially in post-menopausal women. Such women can bring down their risk of breast cancer by limiting saturated and trans-fat intake.
Other than cutting back on fats, the following dietary changes can help lower breast cancer risk:
Genetic testing will tell how harmful fat consumption is for your body. If you are at higher risk of developing breast cancer because of fat intake, talk to a nutritionist to control the risk.
Breast cancer is the most common invasive cancer in women in the developed and developing world. About 5 to 10% of breast cancer cases are inherited.
Inherited breast cancer results from changes or mutations in certain genes that are passed on from a parent. Breast cancer prognosis is better when the cancer is detected in the early stages.
BRCA stands for BReast CAncer gene. More than 1000 different mutations or changes in these genes have been identified to increase breast cancer risk. The role of BRCA genes in breast cancer was first identified in the 1990s. Clinical testing for BRCA mutations gained popularity when Angelina Jolie, who was tested positive for BRCA mutations, underwent preventive surgery to decrease her risk of developing breast and ovarian cancer.
In 2018, the Food and Drug Administration (FDA)approved the reporting of three specific mutations in the BRCA1/BRCA2 genes for breast cancer screening. The FDA-approved markers can be used to identify the risk for breast and ovarian cancer in women, and breast and prostate cancer in men.
In the US, these mutations are found in 2% of people of Ashkenazi (Eastern European) Jewish descent and less than 0.1% of the population overall.
Testing positive for any one of these markers indicates an increased risk of developing breast and ovarian cancers in women and breast and prostate cancers in men. On the other hand, an absence of the three tested mutations does not rule out the chances of developing any of the conditions mentioned above. These three mutations are not very common in the general population.
Changes in the BRCA genes have been linked to an increased risk of breast cancer. Genetic changes can accumulate over time as cells divide. Some of these changes lead to uncontrolled cell division, increasing a person’s risk of developing cancer.
Not all cancers are inherited, but a parent carrying a change in the BRCA genes can pass it on to their children and increase their lifetime risk of developing cancer.
The BRCA1 gene or BReast CAncer 1 gene carries instructions for producing a tumor suppressor protein that helps prevent uncontrolled cell growth and division. This protein also plays a role in repairing damaged DNA, which is crucial for maintaining genome stability.
The BRCA2 gene or BReast CAncer 2 gene is also a tumor suppressor gene.
The name “BRCA” is an abbreviation for the “BReast CAncer gene.” BRCA1 and BRCA2 are two different genes found to impact a person’s chances of developing breast cancer.
Despite what their names might suggest, BRCA genes do not cause breast cancer. These genes normally play a big role in preventing breast cancer.
The BRCA genes carry instructions for the production of proteins that are responsible for preventing uncontrolled cell growth. These proteins are called tumor suppressor proteins. If these proteins do not function properly, it results in uncontrollable growth of cells, which may end up being cancerous.
The BRCA proteins also help repair damaged DNA, thereby maintaining the stability of genetic information. DNA damage can occur due to errors during the DNA replication process or by environmental agents like UV or ionizing radiation.
Certain changes or mutations in the BRCA genes prevent the proteins from doing their job properly and may lead to uncontrolled cell division, increasing a person’s risk of developing cancer. These genetic changes are called harmful or pathogenic variants.
Not all cancers are inherited, but a person carrying a change in the BRCA1 or BRCA2 gene can pass it on to their children and increase their lifetime risk of developing cancer. If either your mother or father has a BRCA1 or BRCA2 gene mutation, you have a 50% chance of having the same gene mutation.
About 1 in every 500 women in the United States has a mutation in either her BRCA1 or BRCA2 gene.
Inherited mutations in the BRCA1 gene are responsible for about 40-45% of hereditary breast cancers.
BRCA2 germline mutations, which are mutations inherited from either parent, are seen in approximately 35% of families with incidences of early-onset breast cancer in their women.
According to the National Cancer Institute, NIH, 55-72% of women who inherit a harmful BRCA1 mutation and 45-69% of women who inherit a harmful BRCA2 mutation will develop breast cancer by 70-80 years of age.
39%-49% of women who inherit a harmful BRCA1 mutation and 11-17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by 70-80 years of age.
Harmful variants in the BRCA1 gene are also linked to a risk of fallopian tube (tubes that connect the ovaries to the uterus) cancer, primary peritoneal cancer that occurs in the lining of the abdomen, pancreatic cancer, and prostate cancer. However, the risk of developing these types of cancer is lower than that of breast cancer.
Mutations in the BRCA genes increase the risk of breast cancer in males too. Men with a BRCA2 gene mutation have a 7 in 100 chance of developing breast cancer, while men with a BRCA1 gene mutation have a 1 in 100 chance of developing breast cancer.
The likelihood of carrying an inherited mutation in BRCA1 or BRCA2 varies across different ethnicities. In the general population, BRCA mutation(s) can be seen in about 1 in 400 people. This number increases to 2 in 100 in people of Ashkenazi Jewish descent. The mutations found in this population are usually one of three FDA-approved variants.
Different population groups also carry different variants - for example, African Americans carry a particular variant in the BRCA1 gene that is not found in the other ethnic groups in the U.S.