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

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

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

What Are The Benefits Of Breastfeeding?

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

Link Between Breastfeeding Duration & Breast Cancer

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

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

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

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

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

Breastfeeding Duration & Breast Cancer

Genetic Factors

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

The XRCC2 Gene

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

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

rs3218536

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

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

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

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

The MDM2 Gene

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

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

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

rs2279744

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

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

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

Non-Genetic Factors

Some factors that influence breast cancer duration include:

Recommendations For Breastfeeding

Increasing Breastfeeding Duration

Breast Cancer Screening

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

Video

Summary

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

References

What Is Breast Cancer Prognosis?

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

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

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

What Is Cancer Survival Rate?

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

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

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

What Is Hazard Ratio?

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

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

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

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

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

Understanding Prognosis

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

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

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

How Genes Influence Breast Cancer Prognosis

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

The RAD51B Gene 

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

rs3784099 

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

Non-Genetic Factors

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

Recommendations to Improve Breast Cancer Prognosis

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

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

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

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

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

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

Video

Summary 

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

References

What is Estrogen Receptor-Positive Breast Cancer? 

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

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

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

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

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

Testing For Hormone Receptors In Breast Cancer

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

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

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

Risk For Er Positive Cancers: Genetic Factors

The BRCA Genes

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

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

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

The CYP19A1 Gene

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

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

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

The ESR1 Gene

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

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

Non-genetic Factors

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

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

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

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

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

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

Recommendations To Reduce Risk Of ER-positive Breast Cancer

Diet

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. 

Exercise

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

Drugs

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

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

BRCA Screening

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

Video

Summary

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

References:

What Are Estrogen Receptors?

Receptors are proteins inside the target cell or on its surface that receive a chemical signal. 

Estrogen is an important hormone responsible for various female characteristics in the body, including the growth and development of breasts (or mammary glands).

Estrogen Receptors (ERs) are a type of steroid receptors that attach to estrogen in the blood and regulate the growth and multiplication of cells in the breast. These receptors pick up signals from the hormones and encourage cell growth. 

In the case of breast cancer, this growth is uncontrollable and eventually becomes cancerous.

Types of Breast Cancer

Based on the presence or absence of estrogen receptors in breast cancer cells, there are two types of breast cancers:

ER-positive

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. 

ER-negative

Breast cancer cells that do not have estrogen receptors are known as estrogen-receptor-negative (or ER-negative) cancers. 

ER-negative breast cancer is less common and more challenging to treat. It also often has poor treatment outcomes.

Knowing whether breast cancer is ER-positive or ER-negative helps doctors plan the appropriate treatment.

Why Should Breast Cancer Be Tested For Hormone Receptors?

Every patient with a breast cancer diagnosis undergoes a hormone receptor evaluation that helps determine if the cancer cells have receptors for estrogen and progesterone. 

About 2 out of every 3 breast cancer cases test positive for hormone receptors. 

Testing breast cancer cells for hormone receptors is important to decide whether hormonal therapy will be an effective course of treatment. 

Hormone therapy involves reducing the estrogen levels in the body or blocking the cells from responding to estrogen. 

Only if the cancer is ER-positive, hormone therapy will work. 

This makes ER-negative cancers difficult to treat; non-hormonal treatments are used for these cancers.

Genetic Factors Increasing The Risk For ER-Negative Breast Cancer

The BRCA2 Gene

The BRCA2  gene provides instructions for producing a protein that acts as a tumor suppressor (proteins that prevent cells from dividing uncontrollably and rapidly). 

The BRCA2 gene is also involved in repairing damaged DNA. 

Changes in the BRCA2 gene can increase the risk of different types of cancers, including breast cancer.

Most women with BRCA2 mutations tend to develop ER-positive breast cancer. However, the prognosis may be worse for these women than for those with ER-negative breast cancer carrying BRCA2 mutations.

The MDM4 Gene

The MDM4 gene is located on chromosome 1 and produces the MDM4 protein, which regulates a tumor suppressor protein called the p53. 

Changes in this gene can affect the protein produced, which in turn interferes with the tumor suppressor activity of p53. 

When this happens, it can lead to uncontrolled cell growth resulting in cancer cell formation. 

The ZNF365 Gene

The ZNF365 gene contains instructions to produce the Zinc Finger Protein 365. This protein plays a role in repairing DNA damage. Changes in this gene increase the risk of breast cancer.

A change in the ZNF365 gene, called 19p13.1,  has been linked to ER-negative breast cancer in individuals with changes in their BRCA1 and BRCA2 genes.

Non-genetic Factors Influencing ER-negative Breast Cancer Risk

Race: There is a higher incidence of ER-negative breast cancers in women of African ancestry.

Obesity:  Pre-menopausal and menopausal women who are overweight or obese are at an increased risk of developing ER-negative breast cancer.

Alcohol consumption: Increased alcohol intake increases the risk of ER-negative breast cancer.

Younger Age: Hormone receptor-negative cancer is more commonly seen in women around 40 years of age who haven’t attained menopause

Recommendations To Reduce Risk Of ER-negative Breast Cancer

Regular Physical Activity

Physically active women who have a healthy weight and lead a healthy lifestyle have a reduced risk of developing ER-negative breast cancer.

Limited Alcohol Consumption

Even low levels of alcohol intake can increase the risk of breast cancer. The ideal upper limit for alcohol consumption to lower breast cancer risk is one drink a day (12-14 grams of alcohol).

Plant-based Diet 

Plant-based diets are packed with fiber, vitamins, and minerals. Fiber helps eliminate excess estrogen (a risk factor for breast cancer). Vitamin C, A, and selenium also play a role in lowering cancer risk. 

A 2013 study that followed approximately 30,000 post-menopausal women with no history of breast cancer for 7 years showed that following these three recommendations resulted in a 62% decreased risk of breast cancer.  

Genetic test for BRCA Mutations

The BRCA genetic test is a blood test that analyses DNA to detect the presence of harmful changes (mutations) in the BRCA1 and BRCA2 genes. Individuals with these mutations are at a high risk of developing breast cancer. Routine testing for these genes in individuals at high risk is recommended.

Video

Summary

  1. Depending on the presence or absence of estrogen receptors on breast cancer cells, breast cancer can be classified as ER-positive or ER-negative.
  2. ER-positive breast cancers form 80% of the total breast cancer cases and are easier to treat with hormonal treatments. ER-negative breast cancers do not respond to hormone therapies.
  3. Knowing the ER status of breast cancer helps the doctor determine the treatment plan for a patient.
  4. The prognosis for women carrying BRCA2 mutations and diagnosed with ER-positive breast cancer is poorer than for those with ER-negative breast cancer. 
  5. Changes in the MDM4 gene can interfere with the tumor suppressor activity of p53 protein, resulting in an increased risk for breast cancer. 
  6. Other factors like race, menopausal status, and alcohol intake influence a woman’s risk of developing ER-negative breast cancer.
  7. Eating a healthy and nutritious plant-based diet, limiting alcohol intake, and being physically active can reduce the risk of ER-negative breast cancer.
  8. BRCA genetic testing can help you assess the risk more precisely and take preventive measures.

References

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.

Genetic Factors Influencing Risk For Breast And Other Cancer

The BRCA1 Gene 

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 

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 

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  

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  

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:

Non-Genetic factors

Exposure To Radiation

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.

Type of Chemotherapy

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. 

Age

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

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.

Recommendations To Bring Down The Risk Of Breast And Other Cancers

Genetic Testing

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.

Analyze The Risks In Your Chemotherapy and Radiation Therapy Procedures 

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.

Adopt Healthy Habits

Some lifestyle changes can lower your risk of developing cancer.

Do Not Fear

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. 

Video

Summary

  1. Breast cancer is associated with a higher risk of developing a second non-breast cancer. 
  2. Certain types of cancer like stomach cancer, colon cancer, uterus cancer, ovarian cancer, sarcoma, and Acute Myeloid Leukemia (AML) can develop after a breast cancer diagnosis.
  3. Both genetic and non-genetic influences increase a breast cancer survivor’s risk for developing other types of cancers.
  4. Abnormal changes in genes like the CHEK2, BRCA1, PTEN, ATM, and TP53 can increase the risk of breast and other cancers. 
  5. Non-genetic factors like age, radiation exposure, the intensity of chemotherapy, and lifestyle habits like smoking also increase the risk of developing second non-breast cancers.
  6. A genetic test can tell you if you are at risk for developing a second non-breast cancer after a breast cancer diagnosis.
  7. Following a healthy lifestyle, keeping away fear, and choosing the right radiation and chemotherapy procedures can help bring down the risk of second cancer considerably. 

References

What Is Radiation?

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 radiationIt consists of two protons and two neutrons. It cannot penetrate past the outer skin and causes no damage
Beta RadiationIt consists of fast-moving electrons. It can penetrate the outer skin and is used to treat superficial tumors.
Gamma RadiationIt 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-raysX-rays are man-made electromagnetic radiation. X-rays are similar to gamma rays and can penetrate the human body.
Neutron radiationIt consists of free neutrons produced in large numbers due to nuclear fission or fusion reactions. 

Sources Of Ionizing Radiation

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.

  1. Cosmic radiation - These rays reach the earth’s surface from the sun and other solar system elements. People living in higher altitudes are more exposed to cosmic radiation. 
  2. Terrestrial radiation - Minerals like uranium, thorium, and potassium, when decayed, release a small amount of ionizing radiation. Some of these minerals are found in materials used for building construction, and hence people may be constantly exposed to minimal amounts of terrestrial radiation in closed spaces.
  3. Radiation exposure through inhalation - Radiation gases like radon, actinon, and thoron are produced due to radioactive mineral decay. Though harmless generally, some closed spaces like mines may have an excess of these gases. 
  4. Radiation exposure through ingestion - Minimal amounts of radioactive minerals are found in drinking water and food cultivated in soil. These reach the human body through ingestion. 

Artificial Sources Of Ionizing Radiation

  1. Medical radiation - Radiation is a standard method to diagnose various health conditions. X-ray machines, Computerized Tomography (CT) scan devices, and particle accelerators are all types of equipment that use ionizing radiation. About 98% of all the artificial sources of ionizing radiation are generated in the medical industry. According to the World Health Organization (WHO), 3600 million diagnostic radiology treatments happen globally using some kind of radiation. 
  2. Nuclear power plants - Nuclear power plants use nuclear reactions to create electricity. Such plants produce ionizing radiation. 
  3. Industries and agriculture - Many industrial and agricultural practices make use of radiation in their everyday processes.

Radiation Exposure As A Breast Cancer Risk Factor

Radiation exposure can cause breast cancer in different ways.

  1. It can alter DNA and lead to abnormal growth and multiplication of cells.
  2. It causes genome instability (changes in genes that can lead to problems in cell growth and multiplication)
  3. It can affect how breast cells interact, multiply, and grow. 

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:

Does Mammography Increase Breast Cancer Risk?

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 Genetic Angle

The H19 Gene

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

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.

GenotypeImplications
AAAssociation between occupational radiation exposure and breast cancer
ACNo association between occupational radiation exposure and breast cancer
CCNo association between occupational radiation exposure and breast cancer

Non-genetic Factors Influencing Radiation Exposure And Breast Cancer Risk

Age

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. 

Excess Exposure to Radiation 

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:

Reproductive History

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

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. 

Limiting Radiation Exposure To Reduce Breast Cancer Risk

Get A Mammogram Only When Absolutely Needed

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. 

Check Your Occupational Exposure To Radiation

Occupational radiation exposure happens in workplaces when the person handles radioactive sources or works with equipment generating radiation. 

Control Other Factors That Lead To Breast Cancer

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.

Opt For Genetic Testing

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.

Video 

Summary

  1. Radiation is the transmission of energy through space or a medium. Non-ionizing radiation is harmless and does not affect the human body. 
  2. Ionizing radiation causes cellular-level changes and can lead to cancer.
  3. Radiation exposure can alter DNA, cause genome instability, affect the way breast cells interact, and lead to breast cancer.
  4. Mammography is a radiation procedure to identify tumor cells in the breasts. Women who undergo excess mammography procedures under the age of 40 may be at a higher risk of developing breast cancer in the future.
  5. Mammography also seems to retrigger second breast cancer in some women who have gone through first breast cancer and radiation therapy before the age of 45. 
  6. Changes in the H19 and ERCC2 genes can increase the risk of breast cancer upon radiation exposure. 
  7. Younger women are at higher risk for developing breast cancer on exposure to radiation. Pregnancy and breastfeeding periods are protective against breast cancer.
  8. Avoiding mammography unless required, using protective shields and gear while working near radiation, and following a healthy lifestyle can all bring down breast cancer risk. 
  9. Genetic testing helps know if a person is at higher risk for breast cancer because of radiation exposure. 

References

How Does Night Shift Work Impact Health?

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.

Night Shift Work—A Risk Factor for Breast Cancer

Some animal studies have shown that exposure to light at night led to the growth of breast cancer.

The risk of breast cancer among nurses and other night-shift workers seems to be higher than their counterparts who worked day shifts. 

For every five years a woman worked the night shift, her risk of developing breast cancer increased by as much as 3.3%

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.

When melatonin levels decrease in the body, it results in an imbalance of inflammatory cytokines, increased mutations in the cells, and oxidative damage (due to free radicals). 

These events can all trigger cancer development. 

A reduction in melatonin also affects estrogen levels, which further increases the risk of breast cancer.

How Does Genetics Influence Rotating Night Shift Work and Breast Cancer Risk?

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 NPAS2 Gene

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.

GenotypeImplication - > 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

Use Xcode Life’s Free Gene Tool To Find Out If You Have The Risk Genotype!

The RORA Gene

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. 

Women who have at least one A allele and had a history of working night shifts in their lifetime had a higher risk of developing breast cancer. 

Conversely, women having the CC genotype and working night shifts showed a decreased risk of breast cancer.

GenotypeImplication
AAIncreased breast cancer risk on night shift work
ACIncreased breast cancer risk on night shift work
CCDecreased breast cancer risk on night shift work

The CRY2 Gene

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.

GenotypeImplication
CGIncreased breast cancer risk on night shift work
GGDecreased breast cancer risk on night shift work
CCDecreased breast cancer risk on night shift work

Regulating Your Sleep-Wake Cycle To Reduce Breast Cancer Risk

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. 

Summary

  1. The circadian rhythm regulates our body’s sleep-wake cycle.
  2. A disturbed circadian rhythm increases the risk of developing health conditions like obesity, cardiovascular diseases, gastrointestinal problems, etc.
  3. According to many studies and published reports, working the night shift is carcinogenic as it decreases melatonin production - melatonin helps stop tumor growth.
  4. Working the night shift has been particularly associated with an increased risk for breast cancer.
  5. Women with certain changes in genes like NPAS2, RORA, and CRY2 have an increased risk of breast cancer when on rotating night shifts.
  6. Regulating your sleep-wake cycle, getting adequate sleep, following a healthy diet, and limiting alcohol consumption and smoking can help lower breast cancer risk. 

Reference:

How Does Exercise 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.

Exercises and Breast Cancer Risk - What Do The Studies Say?

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.

How Does Genetics Influence Exercise And Breast Cancer Risk?

The MTRR Gene

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. 

Previous studies reported the association of this genetic change with lung and colorectal cancers, but not with breast cancer.

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. 

AlleleImplication
THigher risk for hyperinsulinemia and breast cancer when physically inactive
GNormal risk for hyperinsulinemia and breast cancer when physically inactive

The ERCC4 Gene

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.

GenotypeImplication
GGSignificant reduction in breast cancer risk with exercise
AGModest reduction in breast cancer risk with exercise
AANormal risk of breast cancer with exercise

The MLH1 Gene

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.

AlleleImplication
GSignificant reduction in breast cancer risk with physical activity in postmenopausal women
ANormal breast cancer risk with physical activity in postmenopausal women

How To Reduce Your Risk of Breast Cancer with Exercise

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:

Video

Summary

  1. Studies have consistently reported lower breast cancer risk among women who exercise regularly.
  2. Exercising reduces the estrogen levels in the body, thereby reducing your breast cancer risk.
  3. Several studies report a positive effect of exercising, not only on breast cancer risk but also on breast cancer prognosis and survival.
  4. People with a certain genetic type tend to benefit more in terms of breast cancer risk reduction with exercises.
  5. Brisk walking for even 2.5 hours per week could bring down breast cancer risk by 18%!
  6. Aerobic exercises like jogging, cycling, and swimming also seem to be effective in reducing breast cancer risk. 

References:

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. 

How Does Body Weight Affect 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%.

Obesity And Breast Cancer Risk

Obesity and Breast Cancer Risk in Premenopausal Women

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.

Obesity and Breast Cancer Risk in Postmenopausal 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. 

Risk Of Breast Cancer Mortality In Obese Patients

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.

Breast cancer-specific mortality among obese women is 1.3 times higher compared to women with a normal BMI. 

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.

Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk

The BRIP1 Gene

BRCA1 Interacting Helicase 1 (BRIP1) is located on chromosome 17 and, along with the BRCA1 gene, helps repair any damage to the DNA. It is also responsible for maintaining chromosomal stability.

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.

The IGFBP3 Gene

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.

Non-Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk 

Obesity is a critical non-genetic risk factor for breast cancer. 

Other factors that increase breast cancer risk in obese women are:

Does Weight Loss Reduce Breast Cancer Risk?

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.

Recommendations to Reduce Breast Cancer Risk

Summary

  1. Being overweight or obese increases the risk of developing breast cancer. This risk is exceptionally high in postmenopausal women.
  2. An increase in weight increases fat cells in the body and a subsequent rise in estrogen levels. Exposure to estrogen increases the risk of breast cancer development.
  3. Women with BMI over 25 have a higher risk for breast cancer. 
  4. Obese premenopausal women have a lower risk for ER-Positive breast cancer but an increased risk for ER-negative and triple-negative breast cancer.
  5. Breast-cancer-specific mortality among obese women is 1.3 times higher than in women with normal BMI.
  6. Few genes like BRIP1 and IGFBP3 are associated with breast cancer risk in obese women.
  7. Other factors like lack of physical activity, hormone replacement therapy, reproductive history, alcohol consumption, and smoking increase breast cancer risk in obese women.
  8. According to a study, sustained weight loss in women over 50 can help reduce breast cancer risk compared with women whose weight was stable.

References:

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