Ask the Expert

Ask the Expert

New Recommendations for Genetic Testing: How Do I Make Sense Of It All?

During our recent webinar, “New Recommendations for Genetic Testing: How Do I Make Sense Of It All?,” we received a variety of questions, about the impact of genetic testing for our community. Dr. Beth Karlan, Cedars-Sinai Medical Center and Peggy Cottrell, MS, CGC, Sharsheret’s Genetics Program Coordinator, are pleased to answer your questions and concerns below. If you have additional questions and would like to speak with our staff genetic counselor, please contact us at 866.474.2774.

1. Question: I have recently found out I am a BRCA1 carrier. I have heard mixed recommendations of either having a full hysterectomy estrogen hormone therapy or only removing the fallopian tubes and ovaries. How are these decisions generally determined?

Answer: This requires a complex individualized discussion that needs to be personalized for each individual person, based on their individual background. It is important to reach out to your personal medical team to decide on next steps.

2. Question: Is there a value of having a prophylactic oophorectomy to reduce breast cancer risk so that surveillance becomes a real option to avoid prophylactic double mastectomy?

Answer: Yes, Risk-Reducing Salpingo-Oophorectomy reduces breast cancer risk, but not to zero. It would generally not avoid enhanced surveillance. While evidence shows that having the ovaries and fallopian tubes removed well before the age of menopause may reduce breast cancer risk, the evidence is not as strong when the surgery is done closer to the time of natural menopause. Recent studies have questioned the strength of this benefit, so as always, you should look for advice from your physician. The reduction in risk would never be enough to remove the need for high risk screening, which includes an annual breast MRI, annual mammogram/sonogram, and biannual breast exam by a physician.

3. Question: Are there studies that discuss using platinum-based chemo as the first line of treatment?

Answer: Platinum chemo is often considered the standard of care for ovarian cancer, and has been increasing use in breast cancer with germline BRCA mutations.

4. Question: If someone tested negative for BRCA, but later developed breast cancer, is there value to getting more genetic testing looking at a bigger panel of genes, or is it more valuable to use genomic testing of the tumor itself? What are the differences between these options?

Answer: If someone had negative testing in the past, it may be beneficial to consider an updated test. We now do hereditary panels that look at many more genes than were tested in the past. There is a chance that a new test would find something “actionable”,
which means that there would be different recommendations for screening or treatment based on the finding. Tumor testing is totally different. Tumor testing, or profiling, looks at the genetic mistakes, or mutations, which are present in the cancer cells themselves. The benefit of this testing is that it can help the physician determine if targeted therapy may work to treat the cancer. Sometime tumor profiling can give a hint about hereditary mutations that might be present, but it is never a replacement for a hereditary panel.
Technically, the term “genomic” refers to testing all of the genetic information in a person. This term was first used in describing the “human genome project”, in which the entirety of one person’s DNA was first sequenced. A similar term is “exome”, which describes testing of all of the known coding sequences in a person. Sometimes tumor profiling may be called “genomic” profiling because of the large number of genes being tested. It is always important to distinguish hereditary genetic testing from tumor profiling, since either type of test could look at the entire genome.

5. Question: When might a doctor recommend a PARP inhibitor to someone with ovarian cancer?

Answer: For maintenance therapy or treatment as part of a clinical trial. Specifics surrounding use will depend on clinical scenario, and needs to be specifically discussed with your treatment team.

6. Question: Is the BFOR study opened outside of US (ie. CANADA)?

Answer: Not at this time.

7. Question: If I do the BFOR testing do I need other testing done as well?

Answer: It depends. Follow up recommendations are individualized based on family history and other factors.

8. Question: What do the guidelines suggest regarding prophylactic mastectomy for someone who is BRCA1+? Is it the same for BRCA2+?

Answer: Guidelines say that there is evidence to support consideration of a prophylactic, or risk reducing mastectomy for women with either a BRCA1 or BRCA2 mutation. Surgery is not necessary in either case, and women may choose to have high risk screening as an alternative. High risk screening includes an annual mammogram, annual breast sonogram/ultrasound, annual breast MRI, and biannual breast exam by a physician.

9. Question: My father recently died from pancreatic cancer. Are there new recommendations for pancreatic cancer screening?

Answer: Pancreatic cancer screening is difficult, and may not always be beneficial. You should speak with your physician about the available options. It may be best to do pancreatic cancer screening under the auspices of a research study.

10. Question: What are the current guidelines for when to test/at what age to test children of parents who are BRCA positive given current protocols and treatment options if the mother has not gotten any of the cancers?

Answer: Current guidelines do not recommend testing children. Most of the time, there will be no difference in management for someone testing positively for a BRCA1 or BRCA2 mutation until that individual turns 25 years old. It is often best to wait until this age to have testing done. However, every individual and every family is different, so you should look for advice from your own healthcare provider.

11. Question: I had BRCA testing done several years ago. Are there any differences in the BRCA testing now? Are there other gene mutations I should be tested for?

Answer: BRCA testing has changed significantly over the past 30 years. Early on, especially in individual with Ashkenazi Jewish ancestry, testing was done only for founder mutations. Until sometime between 2007 and 2012, testing may or may not have included duplication and deletion testing. Panel testing that included BRCA1 and BRCA2 became available in 2013, but may not have always been ordered by a particular provider. If you have questions about the adequacy of your genetic testing, you should speak to your healthcare provider, or call Sharsheret and make an appointment to speak with me, our genetic counselor. I recently saw a patient who had totally inadequate genetic testing ordered only two years ago, so it is best, even if testing was done recently, to check with your provider.

12. Question: What is the role of oncotype testing in genetic testing & decision making?

Answer: Oncotype testing looks at the genetics of the tumor itself, and is best used to decide about the need for chemotherapy. Oncotype does not give any information about hereditary cancer.

13. Question: What is the frequency of a sporadic mutation causing breast cancer to be BRCA1 or BRCA2?

Answer: We think that sporadic mutations in BRCA1 or BRCA2 leading to breast cancer are relatively uncommon. Most of the time breast tumor genetic testing does not uncover a BRCA mutation. If tumor testing finds a BRCA1 or BRCA2 mutation, germline (hereditary) genetic testing may be indicated.

14. Question: Despite having a strong family history of related cancers, my daughter has not been able to have insurance cover genetic testing for her. Any ideas?

Answer: It may be beneficial to speak to a genetic counselor. There are sometimes insurance issues that can be solved by choosing a different lab. If the insurance issue can’t be solved, genetic testing may be done, at one specific lab, for an out of pocket cash price of $250.

15. Question: Should all Ashkenazi Jews get tested? Why is this test not completed the same time as prenatal genetic screening such as Tay-Sachs?

Answer: It is not unreasonable for all Ashkenazi Jews to consider being tested for BRCA1 and BRCA2 mutations. However, not all individuals are interested in knowing their results. The reason that the test is not included in prenatal genetic screening is that the testing is for something that may cause actual disease in the “carrier”. BRCA1 and BRCA2 testing requires a much more detailed informed consent.

16. Question: I have breast cancer. When diagnosed 5 years ago, based on my and family history, I was told my daughters did not need to do any special or early testing. Has guidance about this changed over time?

Answer: Different national organizations make different recommendations about when to begin breast cancer screening. Most recommend beginning mammograms sometime between 40 and 50 for low risk women. Generally, in the absence of a genetic finding in a family, guidelines recommend beginning breast cancer screening 10 years earlier than the youngest diagnosis in the family. If a person were diagnosed with breast cancer at age 65, their family members should begin screening at the same time as someone in the general population (maybe closer to 40 than 50, but a physician should be consulted). If someone was diagnosed with breast cancer at age 40, their family members might start screening around age 30. When there is a more significant amount of breast cancer in a family, an annual breast MRI may be indicated. Your health care provider can use a computer algorithm to calculate your lifetime risk for breast cancer. If it is 20% or higher, most insurance will cover the cost of the breast MRI. If a family member is diagnosed with breast cancer at a very young age, like 25, we generally do not recommend beginning screening at 15. It is always important to discuss these issues with your own healthcare provider.

17. Question: I am a 72 year old woman of Ashkenazi Jewish heritage. There is no history of related cancers is my family, though my father’s family had many other cancers. Should someone like me consider genetic testing as a preliminary risk screen?

Answer: It depends…you should seek the guidance of a genetic specialist in making this decision. There are hereditary syndromes outside of BRCA1 and BRCA2 that can be present in individuals of Ashkenazi Jewish ancestry. Feel free to set up a time to speak with me at Sharsheret.

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