Nathan Mordel, M.D. »Janet Lefkowitz, D.O. »

Hereditary Genetic CA Screening

July 21, 2017

After losing her mother to ovarian cancer at the age of 56 years old, Angelina Jolie became aware of her up to 87% risk of developing breast cancer and up to a 50% risk of developing ovarian cancer in her lifetime. Upon learning that she tested positive for the BRCA1 gene, Ms. Jolie’s decision to share her choice to undergo an elective double mastectomy in 2013 helped elevate genetic screening exams into our cultural consciousness.

BRCA stands for “breast cancer susceptibility genes.”. In the early 1990’s it was discovered that BRCA1 and BRCA2 proteins are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. However, if BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. Both the BRCA1 and BRCA2 genes have been linked to hereditary breast and ovarian cancers, and research strongly suggests that these defective genes also greatly increase a woman’s chance of developing cancer in her Fallopian tubes and peritoneum as well.

While it is important to know that most breast cancer is not hereditary, up to 25% of inherited breast cancer can be attributed to the BRCA1 and BRCA2 genes. In the United States, approximately 5% of breast cancers and 10-15% of ovarian cancers are hereditary. Hereditary cancer screening for changes in the genes can help steer women toward potentially lifesaving treatments.

In fact, somewhere in the neighborhood of 10% of cancers can be inherited.  The Human Genome Project was a 13-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire human genome. Since its completion in 2003 additional genes have been identified that have a relationship to risk for familial or inherited cancers. In March 2000, President Clinton announced that the genome sequence could not be patented, and should be made freely available to all researchers. The Supreme Court in turn ruled that BRCA1 and BRCA2 are not patentable, since they are “products of nature,” which allows for more companies to devise tests for cancer-causing mutations.  This has allowed for the study of genetics and breast and ovarian cancers to evolve rapidly over the last decade.  And as above, while in the 1990s genetic testing focused most often on the BRCA1 and BRCA2 genes, it is becoming increasingly common to do “panel” or “multi-gene testing.”  This involves multiple other high-risk gene mutations, including BRCA1 and BRCA2.

The evidence on panel testing is still developing. However, some studies have shown it can accurately find BRCA1/2 and other important high-risk mutations that can help manage a person’s breast cancer risk. Because panel testing is still relatively new, the specific set of mutations assessed can vary from test to test. This can have an impact on how results are interpreted and how the information is used.

While at-home testing for gene mutations related to breast cancer is available, The U.S. Food and Drug Administration, U.S. Federal Trade Commission and Centers for Disease Control and Prevention all caution against the use of at-home testing kits.  As with traditional genetic testing, panel testing should only be done in a medical setting after a detailed discussion of risks and benefits with a trained physician or genetics counselor.

Your gynecologist can help address your questions and concerns, and is the first medical professional you should contact regarding inherited female cancers. Based on your personal and family medical history, along with other criteria he or she can determine if you are a candidate for hereditary genetic testing. When looking at your personal and familial health histories (hereditary cancer testing), consider possible indicators of a potential hereditary gene mutation:

  • Several first-degree relatives (mother, father, sisters, brothers, children) with cancer, especially if they’ve had the same type of cancer
  • Cancers in your family that are sometimes linked to a single gene mutation (for instance, breast, ovarian, and pancreatic cancer).
  • Family members who had cancer at a younger age than normal for that type of cancer
  • Close relatives with rare cancers that are linked to inherited cancer syndromes
  • A physical finding that is linked to an inherited cancer (such as having many colon polyps)
  • A known genetic mutation in one or more family members who have already had genetic testing

If screening favors genetics testing, your gynecologist can work with you to get the hereditary genetic cancer testing done.  She or he, and genetic counselors are trained to interpret and explain the test results and what they might mean to you and your family. If a mutation is found, the counselor will talk to you about which of your family members might also be affected.  It will be important for those family members to know exactly which mutation was found and in which gene. They can then discuss this information with their doctors and consider being tested as well.  Your doctor can then more fully discuss treatment options, and help you choose what is right for you.

At AMIGS we offer hereditary cancer screening through a simple, quick and painless salivary sample that is then sent forward to the laboratory for genetic testing. Genetic counseling services are included with the testing, and once results are available, a detailed report is generated, and a plan is constructed to review your potential options. Although genetic testing does not always give you clear answers, it can offer you peace of mind and the knowledge of an important aspect of your personal and family medical histories.

About the Author