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.
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.
Did you know that our ancestors were nocturnal? They used to stay awake in the night to hunt without worrying about dangerous predators and sleep during the day. Now, our circadian rhythms are lined up with the sun. That's why as soon as the sun sets, our bodies start getting ready for rest, and we end up feeling sleepy.
Circadian rhythms are biological cycles that coordinate essential mental and physical functions, such as sleep and hunger. The circadian clock is regulated by a part of the brain called the Suprachiasmatic Nucleus (SCN).
The circadian clock is also influenced by temperature. When the body temperature drops around the afternoon and late evening, it induces drowsiness and sleep.
Sleep is induced by a hormone called melatonin, which is produced in low-light conditions. Bright light conditions during the day suppress melatonin production and promote wakefulness.
People who work the night shift have disrupted circadian rhythm and have an increased risk for the following conditions:
Working the night shift is carcinogenic to humans, according to multiple studies conducted the world over.
Several studies show that disruption in the night’s sleep can reduce melatonin levels and increase the risk of tumor growth.
The risk of breast cancer among nurses and other night-shift workers seems to be higher than their counterparts who worked day shifts.
A study published in the Journal of National Cancer Institute in 2001 reported that women who work in rotating night shifts for at least three nights per month, along with day shifts, have a moderately high risk of breast cancer.
Further, the risk seems to be higher when the night shifts per week increase!
This increased risk is attributed to the messed-up melatonin levels in the body.
In addition to promoting sleep, melatonin also stops tumor growth and protects against the spread of cancer cells.
These events can all trigger cancer development.
A reduction in melatonin also affects estrogen levels, which further increases the risk of breast cancer.
A long duration of shift work throughout the years is associated with estrogen and progesterone-positive tumors.
When the circadian rhythm is altered, it changes the expression of the CLOCK genes. This also influences the production of reproductive hormones.
The Neuronal PAS Domain Protein 2 or NPAS2 gene is the largest circadian gene. It plays a vital role in sleep homeostasis and circadian rhythm regulation.
This gene also regulates the cell cycle and works with certain other genes for repairing DNA. The NPAS2 gene shows a strong association with breast cancer.
rs2305160 (Ala394Thr) is an SNP (Single Nucleotide Polymorphism) in the NPAS2 gene.
Among women with little or no exposure to shift work, the A allele (AA or AG) is associated with a significantly lower risk of breast cancer.
However, among women with AA genotype who had worked >2 years of rotating night shifts, the risk of breast cancer was nearly 3 fold compared to women with the same genotype with <2 years of night shift work.
|Genotype||Implication - > 2 years of rotating night shifts|
|AA (Thr/Thr)||~3 fold increased risk of breast cancer|
|AG (Thr/Ala)||Slightly increased risk of breast cancer|
|GG (Ala/Ala)||Normal risk of breast cancer|
RAR-Related Orphan Receptor A or the RORA gene is located on chromosome 15 and regulates genes involved in the body’s circadian rhythm.
rs1482057 is an SNP in the RORA gene. A study published in 2014 showed that SNP rs1482057 was associated with breast cancer in postmenopausal women.
Conversely, women having the CC genotype and working night shifts showed a decreased risk of breast cancer.
|AA||Increased breast cancer risk on night shift work|
|AC||Increased breast cancer risk on night shift work|
|CC||Decreased breast cancer risk on night shift work|
Cryptochrome circadian regulator 2 or the CRY2 gene gives instructions to produce a protein involved in regulating the body’s circadian rhythm.
rs2292912 is an SNP in the CRY2 gene, located on chromosome 11. Night shift working increased the risk of breast cancer in women who carried the CG genotype of rs2292912 SNP.
|CG||Increased breast cancer risk on night shift work|
|GG||Decreased breast cancer risk on night shift work|
|CC||Decreased breast cancer risk on night shift work|
Since working night shift hours increases the risk of breast cancer in women, one of the most effective ways to lessen this risk is to reduce working night shifts.
Switching with a colleague’s shift, alternating your night shifts with day shifts, or switching jobs can be a few ways by which you can reduce your night shift hours.
Apart from disrupting the sleep-wake cycle, disturbed sleep or poor quality of sleep in people who work night shifts can increase their risk for breast cancer.
So, if you are working a night shift, ensure you get your 7-8 hours of sleep every day. If you have trouble sleeping, consult your doctor about supplements that can help you catch up on your daily sleep.
People working the night shift must try and reduce other risk factors of breast cancer.
A healthy diet with lots of fruits, limited alcohol consumption and smoking, adequate physical activity, and reduced exposure to harmful chemicals can help reduce breast cancer risk.
Regular exercising comes with a range of health benefits, one of which is reduced risk for developing breast cancer. Many studies conducted over the last 20 years have consistently reported a lower risk of breast cancer among women engaging in regular physical activity.
However, the exact mechanism behind this is unclear. Being active may lower estrogen levels in the body. Studies have shown that women with lower blood estrogen levels have a lower risk of breast cancer than women with higher levels.
Adipose tissue is the primary source of estrogen in postmenopausal women. So, reducing body fat with exercise can lower estrogen production and significantly reduce breast cancer risk in postmenopausal women.
In addition, exercise also reduces inflammation in the body, strengthens the immune system, decreases insulin resistance, and reduces oxidative stress – all of which are risk factors for breast cancer development.
A study published in The Journal of the American Medical Association in 2005 reported that physical activity after breast cancer diagnosis might reduce the risk of death due to the disease.
Women who performed physical activity equivalent to walking for 3 to 5 hours per week at an average pace benefited the most.
The study also reported that physical activity after breast cancer diagnosis reduced the chances of recurrence and improved the quality of life in these women.
The primary reason cited for the reduced risk is the low levels of circulating estrogen.
A study conducted in 2015 reported that weight loss by exercise resulted in an increase in lean mass, greater fitness, and a positive effect on the serum sex hormone levels due to greater loss of body fat.
These effects have been associated with a decreased risk of postmenopausal breast cancer.
A systematic review analysis was conducted and published in 2019, wherein researchers studied 38 cohort studies published between 1994 and 2017 comprising 68,416 breast cancer cases.
The researchers observed that the risk for breast cancer was significantly lower in people with exposure to physical activity longer than a year but less than five years, followed by those who had a lifetime exposure to physical activity.
In a study published in 2014, the authors found that breast cancer and colorectal cancer survivors, who increased their physical activity before or after their cancer diagnosis, showed a decreased mortality risk compared with those who were inactive or did not change their physical activity levels.
5-methyltetrahydrofolate-homocysteine methyltransferase reductase or MTRR gene gives instructions for producing the enzyme methionine synthase reductase, which is required for the normal functioning of enzyme methionine synthase.
Certain changes in the MTRR gene can induce insulin resistance, thereby making the cells unresponsive to insulin. This can result in type 2 diabetes.
A 2019 study examined the effect of genetically driven insulin resistance on breast cancer risk.
The researchers identified a Single Nucleotide Polymorphism (SNP) rs13188458 in the MTRR gene. It was found that, in a group of physically inactive people, those with the T allele of this SNP had a greater risk for abnormally high insulin levels (hyperinsulinemia) and breast cancer than people with the G allele.
|T||Higher risk for hyperinsulinemia and breast cancer when physically inactive|
|G||Normal risk for hyperinsulinemia and breast cancer when physically inactive|
ERCC Excision Repair 4, Endonuclease Catalytic Subunit or ERCC4 plays an essential role in repairing damaged DNA. A defect in this gene has been associated with Xeroderma pigmentosa, a skin condition.
A meta-analysis done in 2011 revealed an association between ERCC4 and breast cancer risk. rs1800067 is an SNP in the ERCC4 gene.
Postmenopausal women with the GG genotype of this SNP who engaged in >9.23 hours of recreational physical activity per week experienced statistically significant reductions in breast cancer risk.
|GG||Significant reduction in breast cancer risk with exercise|
|AG||Modest reduction in breast cancer risk with exercise|
|AA||Normal risk of breast cancer with exercise|
The MLH1 or MutL homolog 1 gene is a part of MMR or mismatch repair set of genes. It repairs damaged DNA by replacing the portion containing the errors with the corrected sequence.
rs1799977 is an SNP in the MLH1 gene. Women with the G allele of this SNP who were active during the postmenopausal years experienced significant breast cancer risk reductions.
|G||Significant reduction in breast cancer risk with physical activity in postmenopausal women|
|A||Normal breast cancer risk with physical activity in postmenopausal women|
Researchers have observed that postmenopausal women who exercise for at least 300 minutes per week can successfully reduce their body fat compared to those who spent half that time.
Even 2.5 hours of brisk walking per week can reduce breast cancer by as much as 18%!
If you are in a dilemma about how to begin your exercise, here are some handy and effective tips to help you exercise the right way to keep breast cancer at bay:
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.
Did you know that a person’s chance of developing breast cancer could be genetic? Here’s how it happens.
We inherit DNA from our parents. Our DNA is present within each of the trillions of cells in our body. DNA contains the instruction manual that determines how our bodies function.
Within the DNA, there are thousands of genes that produce all the proteins required by the body. You have two copies of every gene: one from your mum and one from your dad. The mix of your genes is different from that of another person’s. In fact, only identical twins share the same genes.
Sometimes these genes contain faults, called mutations. In most cases, these faults do not have any dangerous effects. But certain mutations alter the proteins that play vital roles in the body. It can disrupt normal development and may lead to medical conditions.
Two genes, BRCA1 and BRCA2, are associated with breast cancer. Contrary to popular belief, these genes don’t cause breast cancer. In fact, they have a protective role against cancers! In some cases, BRCA1 and BRCA2 genes have mutations that interfere with their protective role. Though these mutations may not definitely cause breast cancer, they do increase the chance for it to develop.
A faulty BRCA1 or BRCA2 gene can be passed down from one generation to the next. If either your mum or dad carries a faulty version, then the chance of you having the faulty gene is 50%. Similarly, if you inherit one faulty gene, the chance of you passing it on to each child is 50%. Breast cancer genes cannot skip generations. People who have a family history are estimated to have at least a one-in-ten chance of carrying a faulty gene.
Genetic tests analyze the BRCA gene and help family members find out whether or not they are at increased risk for breast cancer. More than 1,000 mutations in the BRCA1 and BRCA2 genes are known to increase cancer risk.
Xcode Life’s BRCA genetic analysis includes 18 breast cancer-related traits.
Most genetic ancestry companies like 23andMe, provide your DNA information in the form of a text file. This file is called the DNA raw data. Your 23andMe raw data contains several of the BRCA gene markers, which can be analyzed to find out your breast cancer risk. This data looks like a bunch of letters and numbers, which may not make much sense to you.
But, Xcode Life can interpret all this information for you!
All you need to do is upload your raw data and order the BRCA and breast cancer report. Xcode Life then analyzes your raw data in detail to provide you with a comprehensive Breast Cancer Risk analysis.