Decoding the Genetics of Cancer

What Is the Genetics of Breast Cancer?

Breast cancer can run in families sometimes due to certain gene mutations or changes in the genetic structure. The two most common genes related to an increased risk are BRCA1 and BRCA2 (breast cancer genes). When these genes have harmful mutations, they greatly increase your chance of developing breast cancer.

However, having a BRCA mutation does not mean you will get cancer; it just means you are at risk. These mutations are commonly seen in families where most of the members have had breast or ovarian cancer.

Most breast cancers are not caused by inherited gene changes. Instead, they occur due to a mix of lifestyle, environmental, and other genetic factors. There are other, less common gene mutations linked to breast cancer.

In the past, we focused on spotting rare gene variants that had strong effects because they were the easiest to find. However, over the last decade, advances in genomics have revolutionized the field. Now we can look at the entire range of genetic variation. This has helped us better understand inherited cancer risks and what these discoveries mean for cancer biology and treatment.

Genetic testing is recommended for people at risk and who have a family history of breast cancer. The results help you decide on the further screening plan and preventive steps.

What Are Breast Cancer Gene 1 and Breast Cancer Gene 2?

BRCA1 and BRCA2 are the main genes that help repair damaged DNA (deoxyribonucleic acid). Everyone had two copies of each one from their mother and one from their father.

If someone inherits a harmful mutation in either BRCA1 or BRCA2, their risk of developing certain cancers, especially breast and ovarian cancer, goes up a lot. People with these mutations often develop cancer at younger ages than those without them.

Even if a person inherits one mutation in the BRCA gene, they usually still have a working second copy from the other parent. This healthy copy often keeps cells functioning normally and prevents cancer.

But over time, this normal copy becomes damaged or lost due to changes that happen in the body (called somatic changes). When this happens, the risk of cancer increases even more.

What Other Genes Are Linked With Breast Cancer?

Besides BRCA1 and BRCA2, several other genes affect a person’s risk of developing breast cancer. These are as follows:

• PALB2 (Partner and Localizer of BRCA2) Gene: This gene works closely with BRCA2 to repair DNA damage. This increases breast cancer risk for about 35 percent of women by age 70.

• CHEK2 (Checkpoint Kinase 2): This gene helps control cell division and stop tumor growth. The CHEK2 mutation doubles breast cancer risk and makes male breast cancer about 10 times more likely.

• CDH1 (Cadherin 1): This keeps the cells stuck together to form normal tissue. When mutated, it increases the risk of lobular breast cancer, which starts in the milk-producing glands.

• PTEN (Phosphatase and Tensin Homolog): This gene controls how fast cells grow and divide, and helps damaged cells self-destruct before they become cancerous. But when a mutation happens, the cancer risk is high.

• STK11 (Serine/Threonine Kinase 11): A tumor suppressor gene whose mutation causes Peutz-Jeghers syndrome, a condition that increases the risk of various cancers, including breast cancer.

• TP53 (Tumor Protein P53): It is often called the guardian of the genome. TP53 detects DNA damage and either repairs it or destroys the affected cell. Mutations in these genes prevent damaged cells from dying, allowing cancer to develop. Some TP53 mutations are inherited, but most occur during a person’s lifetime.

How to Know if I Have a Genetic Mutation?

The only way to know for sure if you have a genetic mutation linked to a higher risk of breast cancer is through genetic testing. Your doctor helps you choose the right test based on your personal and family history of breast cancer or other cancers.

A few things that can help you know if you have genetic mutations are as follows:

• There is a known breast cancer gene mutation in your family.

• You or a family member was diagnosed with breast cancer before age 50, or had two separate breast cancers.

• A family member had triple-negative breast cancer.

• If anyone in the family had ovarian, pancreatic, or high-risk prostate cancer.

• You have Ashkenazi Jewish ancestry.

• Multiple relatives on either side of your family have had breast cancer at any age.

What Tests Can Detect Breast Cancer Genes?

Genetic testing is used to determine any abnormality in the genes, chromosomes, and DNA proteins. In breast cancer, the test is used to identify gene-expression profiling. This test helps classify breast cancer into various intrinsic subtypes based on how certain genes are turned on or off. When scientists study these patterns, they group breast tumors into five main subtypes. They are as follows:

1. The normal-like subtype, which looks similar to healthy breast tissue.

2. Two luminal subtypes (luminal A and B) that come from luminal cells and usually express the estrogen receptor (ER).

3. A basal subtype, which comes from cells in the basal layer and typically does not express the ER.

4. A HER2-enriched type, which shows high levels of the HER2 growth receptor.

Each subtype behaves differently, has its own typical appearance under the microscope, and is linked with its own survival outlook.

What Is Emerging Research in Breast Cancer Genetics?

Emerging research in breast cancer genetics is moving beyond the well-known BRCA1 and BRCA2 genes. Scientists are now studying polygenic risk scores, which combine information from many genes to better predict a person’s overall risk of breast cancer. New large-scale genetic studies involve a group of people from various backgrounds to discover new risk genes, helping fill research gaps that were once focused on a specific population.

At the same time, tools like liquid biopsy and circulating tumor DNA (deoxyribonucleic acid) are being explored to identify early signs of cancer recurrence or leftover cells after treatment.

Advances in functional genomic and multi-omics that study how genes and other biological systems interact are revealing how both genetic and non-genetic factors affect how tumors grow and respond.

What Is Genomic Testing for Breast Cancer?

Genomic tests, also known as genomic assays, examine a sample of cancer tissue to see how active certain genes are. The level of gene activity helps predict how likely the cancer is to spread and grow.

Genomic testing checks specific genes in a cancer tumor to see how they are and whether they have any mutations. This helps the doctors understand how likely the cancer is to come back and which treatments help in reducing that risk. Depending on the results, your oncologist will suggest chemotherapy or radiation after surgery, or decide how long hormonal therapy must go on.

Genomic tests are also called gene expression profiling tests, and they are a type of biomarker test used to better understand how a tumor might behave and respond to treatment. There are seven genomic testing types-

1. Breast cancer index.

2. DCISion RT (a test that helps doctors personalize the treatment plan).

3. Endopredict test.

4. Mammaprint.

5. Oncotype DX breast recurrence score.

6. Oncotype DX breast DCIS (ductal carcinoma in situ) score.

7. Prosigna (PAM50) test (a test that analyzes the cancer genes).

Conclusion:

The role of genetics is predominant in cancer occurrence, both in inherited and tumor-based gene changes that affect risk and treatment. Genetic and genomic testing help identify gene mutations in specific genes. There are several different genes involved, but BRCA1 and BRCA2 are the most common. Emerging research helps in personalized treatment plans, prevention, and prediction of recurrence.

Key Takeaway/Note From iCliniq:

• Gene mutation in the BRCA1 and BRCA2 genes increases the risk of breast cancer.

• Genetic and genomic testing help in diagnosis, risk prediction, and treatment planning of breast cancer.

• Emerging research and genomics, like liquid biopsies, help doctors understand cancer type and risk. If you have a family history or risk of cancer, consult a breast cancer specialist at iCliniq.