Genetic Mutations

In the mid 1990’s, scientists identified two genetic mutations that harbor an increased risk for developing breast and ovarian cancer. These mutations, known as BRCA1 and BRCA2, can be found in both men and women. While they tend to be the most well-known and widely discussed mutations when it comes to breast and reproductive cancers, they are not the only genes that can impact your risk of developing breast cancer.

Over the past ten years, researchers have identified several other genes which are linked to an increased risk of breast cancer. These include mutations in ATM, CHEK2, PALB2, PTEN, and TP53 genes, among others. A complete breast cancer panel now includes these more recently discovered mutations. Patients who were tested before 2014 should consider re-testing in order to receive more complete information.

Patients living with gene mutations or other risk factors are known as previvors. This high-risk group typically undergoes increased breast cancer screening. Many consider risk-reducing mastectomies.

BRCA1 and BRCA2 Gene Mutations

BRCA1 and BRCA2 genes are part of a DNA repair pathway that corrects naturally occurring mistakes in DNA replication in breast cells. When these genes have harmful mutations, they fail to function properly, which impedes DNA repair and increases the risk of cancer development.

A breast cancer panel can detect these hereditary mutations using a simple blood test. Other moderate risk genes in the same pathway include CHEK2, PALB2, PTEN, TP53, CDH1, and ATM. A breast cancer panel tests the whole pathway.

The presence of harmful BRCA1 or BRCA2 gene mutations does not guarantee that breast cancer will develop (just as the absence of harmful BRCA1 or BRCA2 gene mutations does not guarantee that cancer will not develop). However, those who carry the mutations have a significantly increased risk of developing breast cancer.

Reports indicate that the increased risk is 55 to 65% for BRCA1 mutation carriers and 45 to 55% for BRCA2 mutation carriers. That means that individuals who carry those mutations are 45-65% more likely to develop breast cancer than the average member of the population. The population risk for breast cancer is about 12%.

Risk Factors for Genetic Mutations

Most cancer is sporadic, meaning that it does not come from genes or family. By the same token, cancer that runs in families is not necessarily genetic. Hereditary (genetic) cancers tend to have specific features.

Risk factors for having a gene mutation include:

  • Having another family member that has tested positive for a BRCA gene mutation
  • Having had early onset breast or ovarian cancer (diagnosed before age 45)
  • Having a family history of early onset breast cancer
  • Having Eastern European or Ashkenazi Jewish heritage
  • Usual events, like male breast cancer
  • Having multiple sites of primary cancer (e.g. breast and pancreatic cancer)

Individuals with the risk factors above may want to speak to a doctor about genetic testing to determine whether a harmful mutation is present. A breast surgeon or gynecologist can help you determine if you are considered high risk. A genetic counselor can help you understand your risks and guide decision-making. Insurance should cover testing for anyone who meets criteria that place them in a high-risk category.

If you have a harmful genetic mutation, your breast surgeon or oncologist can help direct your treatment options. These include the use of risk-lowering medications, such as Tamoxifen and raloxifene, both of which may reduce the risk of developing estrogen-receptor positive breast cancers. A more definitive option is risk-reducing mastectectomy. Most people who choose risk-reducing mastectomy also choose to have immediate breast reconstruction.

Mental Health and Non-medical Considerations

Some patients find the decisions surrounding genetic testing to be emotionally overwhelming. Your doctor or genetic counselor should inform you of the risks associated with testing either positive or negative for a gene mutation. Patients with a strong family history, including those with multiple family members diagnosed with breast cancer, may still test negative for all known genetic mutations.

Genetic test results are not a diagnosis. A negative test result does not entirely eliminate the chance of developing breast cancer. Patients without gene mutations still carry a population risk. A positive test does not mean that you have or will develop cancer in your lifetime.

Patients should also be counseled on the non-medical issues associated with genetic testing. Health insurance carriers in the United States are prohibited from discriminating against patients that test positive for a harmful gene mutation. However, life insurance carriers have no such restrictions. This may have less of an impact on a patient already diagnosed with breast cancer, but it can pose a risk for family members who want to get tested.

Testing Before Surgery

Patients who have already been diagnosed with breast cancer may choose to have genetic testing done prior to making any final surgical decisions. Results can help inform procedure type (lumpectomy vs. mastectomy) and whether a patient should consider a contralateral risk-reducing mastectomy.

Risk-Reducing Procedures

A risk-reducing mastectomy is a mastectomy performed on a high-risk patient who has not been diagnosed with breast cancer. It reduces the chance of developing the disease.

High risk patients who have not been diagnosed with breast cancer may undergo genetic testing to help determine a preventative course of action. In some cases, bilateral risk-reducing mastectomies may be recommended.

Risk-reducing mastectomies reduce breast cancer risk by over 90% in patients who do not have a cancer diagnosis but carry a harmful gene mutation. Many high-risk people find peace of mind through risk-reducing surgeries, which can eliminate frequent surveillance, numerous biopsies, and fear of developing cancer. Surgery empowers these patients to feel that they have taken control and done everything in their power to reduce their risk of developing breast cancer.

Patients who choose monitoring over surgery can expect recommended screening through MRI, ultrasound, and mammography every three to six months.

Breast reconstruction availability and quality can help patients make this intensely personal decision. Immediate breast reconstruction and new, nipple and areola sparing mastectomy techniques mean that patients can wake up with natural-looking, reconstructed breasts right after surgery. These types of options can reduce the emotional impact of mastectomy. Knowing your breast reconstruction options early in the process can inform your decisions about the choice and timing of risk-reducing mastectomy.

Bilateral Risk-reducing Mastectomy

A bilateral risk-reducing mastectomy is when a high-risk patient removes both of their breasts to reduce their risk of breast cancer.

Bilateral risk-reducing mastectomy removes both breasts to reduce a high-risk patient’s chances of developing breast cancer. This option suits people who have an inherited genetic mutation that increases the risk of developing cancer who prefer to avoid rigorous screening. In most cases, the nipple and areola can be preserved. Patients who undergo bilateral risk-reducing mastectomy can generally plan an immediate breast reconstruction.

Contralateral Risk-reducing Mastectomy

A contralateral risk-reducing mastectomy is when a patient who has had cancer in one breast chooses to remove their other breast to reduce their risk of breast cancer recurrence.

People with a harmful genetic mutation who also have breast cancer can have a risk-reducing mastectomy to remove the opposite healthy breast at the same time as their cancer surgery. This procedure is called a contralateral risk-reducing mastectomy. In most cases, this can be coordinated with immediate breast reconstruction.