Understanding Genetic Testing

A gene mutation simply means there is a change from the reference DNA sequence. To disprove the inaccurate assumption that every gene mutation is harmful or disease-causing, the genetics community worked to specifically define genetic changes to help clearly communicate whether certain genetic mutations are harmful or just simply exist without impacts. This movement lead to retiring the term “mutation” and replace it with the more impartial noun “variant.” The intent is for “variant” to remain a neutral term, but variant classifications are applied to single gene conditions and include the following categories: pathogenic, likely pathogenic, uncertain significance, likely benign, or benign. Pathogenic variants place individuals at a higher risk for developing cancer. Learn more about this update in terminology and other BRCA terminology.

I have already had genetic testing, so what does a positive result mean?

For both males and females, a positive genetic test result means that a harmful (pathogenic) mutation has been detected in one or more of the genes on the genetic testing panel that increases your risk of certain cancers. The genetic result report will indicate which gene/s have a pathogenic mutation and the specific mutation location. This result means that you have increased cancer risks and need to be managed differently. Once a cancer risk gene mutation has been found in a family, relatives may wish to consider genetic testing to better understand their risk for cancer.

Learn More

What are some other hereditary cancer gene mutations and what should I know about them?

What are the cancer risks for people with mutations in BRCA1 and BRCA2?

Cancer risks are gene dependent. This means that the risk for a specific type of cancer and the estimated future lifetime risks for those cancers can vary gene to gene. When an individual undergoes genetic testing and a BRCA1 and/or BRCA2 gene mutation is identified , this means that they have an inherited mutation that puts them at increased risk for certain cancers. The cancer risks associated with BRCA1 and BRCA2 gene mutations are presented as ranges (see table below), since cancer risk may vary in different families or population groups. Some studies and laboratories report slightly higher or lower risks than what is summarized in the table.

If you are determined to be a carrier of a BRCA1 and/or BRCA2 pathogenic gene mutation, this means that a person who inherited a mutation in either gene and is at increased risk for certain cancers. The cancers most commonly associated with BRCA mutations are breast (male and female), ovarian, prostate and pancreatic cancers, as well as melanoma. The cancer risks associated with BRCA1 and BRCA2 in men and women carrying mutations are presented as ranges.

Cancer Risk Ranges for BRCA1 and BRCA2 gene mutation carriers

[INSERT RISK GRAPH - TO BE UPDATED]

Why are cancer risks presented as ranges? Why are cancer risks different, depending on the source?

The cancer risks associated with BRCA1 and BRCA2 in men and women carrying mutations are presented as ranges since cancer risk may vary in different families or population groups. As more individuals undergo genetic testing and more studies to assess cancer risk are published, our understanding of cancer risk in individuals with BRCA1 and BRCA2 mutations will continue to evolve. For these reasons, risk estimates may vary from one source to the next and as research advances.

Where in the range of risk do I fall?

At this time, we cannot predict where any individual will fall in the risk range. There are other genetic and lifestyle factors that can influence or modify cancer risk associated with mutations in BRCA1 and BRCA2. Discovering these factors and refining our understanding of the risk associated with them may help us provide a more accurate individual risk assessment. The Basser Center is actively working on studies to uncover the factors that may help individualize risk assessment.

Do all people with BRCA mutations develop cancer?

People with mutations in BRCA1 or BRCA2 may develop one or more cancers, or they may not develop cancer at all. Unfortunately, being diagnosed with one type of cancer does not mean that other cancer risks no longer apply. For example, women with a BRCA mutation with breast cancer are at increased risk of developing a second new breast cancer and other cancers.

I have tested positive for a gene mutation, but I already have cancer. What should I do?

Genetics is a constantly evolving field. Questions about testing for additional genes that may increase cancer risk should be directed to your genetic provider. If you had genetic testing 10+ years ago ask a genetic counselor if you are a candidate for updated testing.

If you have recently tested positive for BRCA1, BRCA2 or other hereditary cancer gene mutations, please call please call 215-349-9093 to learn more from a provider trained in genetics at Penn Medicine’s MacDonald Cancer Risk Evaluation Program. 

You can also search the National Society of Genetic Counselors 'Find a Genetic Counselor' tool or contact your local cancer center. Genetic counselors who perform BRCA testing are often a part of the breast group of academic medical centers or cancer centers and may be able to connect you with a physician with expertise in hereditary cancer for medical management guidance.

Are there other cancer risks for BRCA mutation carriers?

In addition to the cancers commonly associated with BRCA mutations (breast, ovarian, prostate, pancreatic, melanoma), men and women with BRCA mutations appear to have a slightly increased risk of developing cancers in general. Therefore, regular medical follow-up with prompt attention to symptoms is strongly encouraged. For example, unexplained weight loss, unexplained and persistent pain, swollen lymph nodes, and sores that do not heal should be evaluated by a physician.

General cancer screening recommendations, such as colonoscopy and cervical cancer screenings, should also be followed in addition to the more intensive cancer screening recommended for BRCA1 and BRCA2-related cancers.

What is cancer risk management?

A personalized cancer risk management program can be developed for individuals known to be at increased cancer risk due to a mutation in BRCA1 or BRCA2 or other hereditary cancer risk genes. You and your doctors will ultimately decide what plan makes the most sense for you. To find an NCI-Designated Cancer Center near you and to learn more about each center's specific research capabilities and programs, including clinical cancer genetics programs, visit the National Cancer Institute website.

Cancer risk management generally includes the following categories:

• Intensive screening to increase the chances of early detection, should cancer develop.
• Prophylactic or risk reducing surgical removal of ovaries and consideration of prophylactic removal of the breasts.
• Chemoprevention, which is taking a medicine shown to lower the chances of developing cancer.

What cancer screenings are recommended for men and women with a BRCA mutation?

View the current guidelines for cancer screenings on our website.

[OR ADD IN NEW TABLE - TO BE UPDATED!!!]

Our website includes the BRCA resources you need to answer your questions related to BRCA gene mutations. The Basser Center offers individuals and families affected by hereditary cancer support through patient stories, blogs, video, and more. We also offer a list of trusted partners and organizations that can connect you to support networks and additional services.

It's important to share important hereditary health information with family members. For suggestions on how to communicate with family members about hereditary cancer risks and care, please read our family letter. 
 

View Family Letter Example