By Athena Puski, MS LGC
Licensed Genetic Counselor
Holden Comprehensive Cancer Center University of Iowa Hospitals and Clinics

You’ve probably heard of BRCA1 and BRCA2, or “the BRACA genes,” which increase the risk of getting breast and ovarian cancer. But have you heard of PALB2, CHEK2, or ATM? Many are surprised to learn there are 11 additional genes besides BRCA1 and BRCA2 that are known to increase the risk of getting breast cancer, and many more genes are still being researched for their possible association with hereditary breast cancer.

A mutation in any of these “other” genes increases the chance of getting breast cancer. Some increase the risk for breast cancer just a little bit, while others increase the risk a lot. These genes can also increase the chance of getting other cancers besides just breast cancer. For example, CHEK2 mutations slightly increase the risk for breast cancer and colon cancer, while PALB2 mutations slightly increase the risk for pancreatic cancer, ovarian cancer, and breast cancer.

Knowing if you have one of these genetic mutations can impact medical care for you and your family members. There are often steps that can be taken to detect cancer at an early and more-treatable stage, or even prevent cancer. How this is done depends on the specific gene in which there is a mutation. It may include screening for cancer more often, such as doing a mammogram and a breast MRI every year. Sometimes surgery can be used to prevent cancer, such as by removing the ovaries or both breasts. Medications can also sometimes be used to lower the chance of getting cancer. In some cases, targeted cancer treatments, such as PARP inhibitors, can be used as part of the treatment for breast cancer.

These hereditary causes of cancer are not common—only about 10% of all breast cancers are estimated to be due to an inherited genetic mutation (about half of which are due to a mutation in a gene other than BRCA1 or BRCA2). Those with a genetic mutation often (but not always) have a strong family history of cancer. Some things that can indicate you might have a hereditary breast cancer condition and may want to consider genetic testing include the following:
• You or someone in your family had breast cancer before the age of 45
• You or someone in your family has had triplenegative breast cancer, ovarian cancer, pancreatic cancer, male breast cancer, or metastatic prostate cancer
• At least three members of your family have had breast cancer or prostate cancer at any age

If genetic testing is something you are interested in learning more about, talk with your doctor or a genetic counselor. Even if you had BRCA1 and BRCA2 genetic testing in the past, additional testing for mutations in other genes may be appropriate. This type of genetic testing is called “update testing” or “panel testing.”

Genetic testing can usually be done with a blood sample or sometimes a saliva sample. Nowadays, insurance coverage for genetic testing is often very good. However, even if insurance won’t cover the cost of testing for you, there are routes available to get genetic testing for about $250, even without insurance. Genetic testing isn’t right for everyone, though, and that’s okay. It is scary to learn you and family members have an increased chance of getting cancer; not everyone is ready for this information. Others may welcome the information learned from genetic testing so they can take proactive steps against their cancer risk. A genetic counselor and your doctor can help you determine what is best for you. FORCE (https://www.facingourrisk.org/) is also great resource to learn more about genetic testing and genetic mutations.

Whether or not you decide if genetic testing is right for you, knowing your family history is key. The upcoming holidays are a great time to talk with family members and gather their medical history. Here is a guide to help you through the process about asking family members about their health history: guide-tofamily-health-history.pdf (geisinger.org).

by Jeanne Olson, RN

​Genetic testing has expanded greatly in the past few years. BRCA1 & BRCA2 were the only genes tested for breast cancer in the past. Genetic testing panels are now standard. Only one out of ten (10%) women diagnosed with breast cancer have a genetic predisposition measurable by genetic testing.

Genes related to breast cancer development now include ATM, CDH1, CHEK2, PALB2, PTEN, STK11, TP53, NBN, NF1, in addition to BRCA1 & BRCA2. All of these genes have a different penetrance level, there are varying percentages of risk.

Cancer genetic panel testing also include the genes for cancers affecting colon/gastric, pancreatic, prostate, melanoma, ovarian/uterine and others. Most genes affect more than one body system.

The American Society of Breast Surgeons (ASBS) published a consensus statement this spring, stating all women with a diagnosis of breast cancer, regardless of age should be genetically tested. For those women who were tested previously only for BRCA1 & 2, they should be offered updated panel testing. It is felt that of the 10% noted above, only half of those were being identified due to the restrictive insurance company policies.
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Genetic testing is offered locally at the cancer treatment centers, as well as the breast centers, and some primary care offices. Samples of either blood or saliva can be submitted for DNA sampling.

If you were tested for BRCA1 & BRCA2 only in the past, check with your physician about having expanded panel testing.
Genetic testing results fall into three categories: A positive/pathogenic variant, a negative result and then variants of uncertain significance (VUS).
• For those with a positive/pathogenic variant, genetic counseling is recommended. Genetic counseling can be obtained by an in-person visit – typically in Cedar Rapids, Iowa City or Mayo Clinic.
The Genetic testing companies may also offer genetic counseling via phone with a certified genetic counselor.

• A negative result is reassuring, but it doesn’t mean the patient is “off the hook” for developing any of the cancers affiliated with the genes tested, but it does mean the patient does not have a genetic predisposition to that cancer development.

• VUS – variant of uncertain significance is essentially a negative report. These variants are not actionable. VUS are followed by the genetic testing companies and over time, some of these will be upgraded to a positive/pathogenic variant, others may be downgraded to negative. When there are changes to a VUS, the ordering physician is notified. That provider’s office will notify the patient of the change. Inheriting a positive/pathogetic variant, for many of the common cancer genes, is a 50/50 chance.

If a patient is negative, her children are negative. If a patient is positive, her children would have a 50% chance of also having the same gene mutation. Costs have decreased dramatically as well. $4,000 was a commonly billed amount in the past.

Some companies will provide testing for $250 or possibly less. There is significant market share competition with the various testing companies, each have their own offers. Health insurance providers are prohibited by law from discriminating against patients with a pathologic genetic variant. This same protection is not available for life, disability and long-term care insurance.

When a patient is seeking genetic testing and has not had a cancer diagnosis, it is recommended they have these insurance policies in place before testing. Not disclosing genetic testing results on applications is fraud, a criminal offense. There are reports of Medicare fraud, where patients are contacted unsolicited, usually by phone, telling them because they have had breast cancer, they can be tested from home.

These fraudulent callers already have the patient’s Medicare number and other demographic information. If the patient agrees, a kit is sent to them, once returned, some do get a report. But there are instances of Medicare paying for the testing, but the patient never receiving a report.

​The Office of Inspector General (OIG) has open cases regarding this fraudulent activity, including locally. The recommendation is to always have your testing with a medical provider. Do not accept phone calls offering testing. The genetic/ancestry testing that is commercially available is also not recommended as those labs are not accredited with Clinical Laboratory Improvement Amendments (CLIA).
To read the complete consensus statement of the American Society of Breast Surgeons (ASBS) issued this spring can be found at https://www.breastsurgeons.org /docs/statements/ConsensusGuideline-on-Genetic-Testingfor-Hereditary-BreastCancer.pdf
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