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.
According to a research study by the University of Exeter Medical School in the United Kingdom, men with hemochromatosis, a common genetic disorder due to iron build-up, are ten times more likely to develop liver cancer.
Hemochromatosis, also called the iron-overload disease, is a condition where too much iron builds up in the body. Usually, the intestines absorb adequate amounts of iron and excrete the rest.
With hemochromatosis, excess iron is absorbed by the intestines, and the body has no way of getting rid of it. As a result, iron gets built up in joints, the pituitary gland, and organs like the liver, heart, and pancreas.
This gradually results in the shutting down of these organs if hemochromatosis is not treated.
Hemochromatosis is more serious in men. Women may be partially protected as they lose some iron during menstruation and childbirth.
Some common symptoms associated with hemochromatosis include:
HFE gene is associated with iron homeostasis. A variant (type) of the HFE gene, called the C282Y (the faulty type), is significantly associated with hereditary hemochromatosis.
According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins.
With hemochromatosis, the iron build-up is commonly seen in the liver. This enlarges the liver and messes up the liver enzymes. It can result in an increased risk of liver conditions like cirrhosis, fibrosis, and cancer.
Hepatocellular carcinoma (HCC), a primary form of liver cancer, was the first condition in which hepatic iron overload was shown to predispose to the development of HCC.
According to a study, 8-10% of people with hemochromatosis develop HCC.
The study was led by the University of Exeter Medical School along with the University of Connecticut, Western University in Ontario, and South Warwickshire NHS Foundation Trust.
This study focused on men and women with two copies of the faulty HFE gene - C282Y. The data of 2890 people aged 40-70 years were analyzed over a nine-year period.
The following were observed:
The study insists on the importance of early diagnosis of hemochromatosis in order to avoid health complications and even death.
The NHS advises that “it is important to talk to your GP if you have a parent or sibling with hemochromatosis, even if you don’t have symptoms yourself” to identify your risk.
The lack of impact on women from the faulty HFE gene variant may suggest that periodic blood donations might play a protective role.