Q&A From Genetics Webinar: Beyond BRCA: Myths and Facts about Your Cancer Risk (December 9, 2020)
Thank you for attending our genetics webinar. Below are questions that were submitted before and during the webinar. Some questions were similar, so I grouped them together and made a common answer. I have answered to the best of my ability for typical situations, but please remember to discuss all of your specific concerns with your own health care providers. If you need further information, please do not hesitate to contact me at Sharsheret, and I will be happy to discuss the specifics of your situation.
We have received many questions, which have been divided into topics. 1) BRCA1 and BRCA2, 2) Other cancer genes, 3) Other types of cancer, 4) Testing, Interpretation of Testing and Retesting, 5) Screening and, 6) Miscellaneous.
BRCA1 and BRCA2
- What annual screening should BRCA1 or BRCA2 people do every year?
Based on national guidelines, women with hereditary BRCA1 or BRCA2 mutations should have high risk screening for breast cancer including an annual MRI beginning at age 25. They may consider the option for a prophylactic bilateral mastectomy. There is an increased risk for ovarian cancer, approximately a 27-44% lifetime risk with BRCA1, and a 15-25% risk with BRCA2. There is no effective screening for ovarian cancer. With BRCA1, the recommended surgery is usually a total hysterectomy including ovaries and tubes, between the ages of 35 and 40. With BRCA2, the recommended surgery is usually removal of the ovaries and tubes, between the ages of 40 and 45. These recommendations typically are made even for women without a family history of cancer. Those with a family history of pancreatic cancer should consider pancreatic cancer screening (see question 17).
- What other types of cancer risk are associated with BRCA other than breast cancer and ovarian cancer?
I am BRCA2+ and I know we are at increased risk for breast, ovarian and melanoma. I see other cancers seem to be added as well, but what others are we really at a higher risk for other than those listed above?
I have the BRCA2 gene and have had a prophylactic mastectomy and have had my ovaries removed. Wanting to know if there is a test that would show a predisposition for pancreatic cancer.
What screenings are recommended for BRCA1 who have had all the preventative surgeries? Are there any recommended screenings for pancreatic cancer, even if no family history?
What about screening for the other cancers that BRCA2 puts you at high risk for?
Individuals who carry mutations in BRCA1 and BRCA2 may be at increased risk for other cancers. National guidelines recommend a skin exam by a dermatologist; mainly BRCA2 carriers are at an increased risk for melanoma. Those with a family history of pancreatic cancer should consider pancreatic cancer screening (see question 17). Those with no family history should discuss pancreatic screening with their physician. Men should also consider screening for prostate and male breast cancer (see question 3).
- I would ask that breast cancer in men be discussed. So many women and men have no idea that men can pass along the risk to their children.
How about men with the BRCA1 gene? What should they do? Do they qualify for high risk breast MRI each year?
Any genetic connection to testicular cancer?
Men who have had breast cancer should consider updated testing, as other genes other than BRCA1 or BRCA2 may increase male breast cancer risk. Those men who know they are carriers of a mutation should check their own breasts and have an annual breast exam by their doctor. Ask your doctor about breast imaging; there is no agreement about the benefit of screening mammograms. Careful screening for prostate cancer should begin around age 35-40. Consider an annual skin exam by a dermatologist. Those with a family history of pancreatic cancer should consider pancreatic cancer screening (see question 17). Testicular cancer may be hereditary, but is not associated with any of the genes we currently test for in panel testing.
- What percentage of BRCA go ahead with risk reducing surgery, either breast or ovarian (or both), and when? If they opt not to go this route, how do they fare?
I am not aware of any available data to answer this question. However, both high risk screening and prophylactic bilateral mastectomy are effective choices that women make. Women who decline prophylactic bilateral mastectomy do very well as long as they have an annual MRI added to their screening regimen. They are more likely to be diagnosed with breast cancer at some point, since breast cancer screening does not prevent cancer. However, they are much more likely to have better outcomes than those who don’t have an annual breast MRI since they are often diagnosed at an earlier stage.
- I have 2 teenage sons with my BRCA1 How do I teach them to be cancer proactive? Does the mutation stop with them (can they pass it to their offspring)?
What age and which tests are recommended for daughters of a BRCA cancer survivor?
At what age is it recommended to get tested?
Families differ on the age at which they discuss cancer mutations with their children. However, the medical community strongly suggests that unless there is a rare mutation in a family that causes cancer in children, genetic testing should be reserved for adults. Once you are 18, you are old enough to be tested, but 25 is the age when there is something different to be done in those who are carriers.
It is important for all parents to teach their children how to take care of themselves. We model what it means to eat a healthy diet, exercise, avoid smoking and excess drinking and have regular visits to the doctor. There is often not a lot of value to discussing specific management of hereditary cancer with teenagers. These discussions should wait until they are ready to have testing as adults.
It is also important to remember that males or females that inherit a mutation can pass it along to either male or female offspring.
- I have a BRCA2 mutation, and had a second primary in my less than 5% breast tissue 15 years after my mastectomy. Does that mean that in any remaining breast tissue cells I still have an 87% chance of breast cancer?
No, statistics are very confusing. It is rare to have a second primary cancer after a mastectomy, and it would be even rarer to have it happen twice. The risk is not for each cell, but for you as a person. Also, the risk is never as high as 87% for a person who is older, or who has already had cancer.
- I had invasive ductal carcinoma treated by a lumpectomy. Years later, a BRCA mutation was identified, and a prophylactic double mastectomy found bilateral LCIS, explained as “markers” . LCIS is not as familiar, more vaguely defined, could you define? Thank you for all you do.
LCIS (lobular carcinoma in situ) is not the same as DCIS (ductal carcinoma in situ). It is not likely to turn into cancer. However, its presence is a marker that indicates a higher risk for that person to develop breast cancer. It is much less important when it is found in a mastectomy specimen, since that procedure has so significantly reduced risk of recurrence.
- If a person is BRCA positive and has had ovarian cancer, how likely is she to get breast cancer?
Breast cancer and ovarian cancer are separate events, and so we think that the risks are therefore separate and not affected by the development of one or the other first. However, some studies have shown that women who are diagnosed first with ovarian cancer may have a somewhat reduced risk for breast cancer. Scientists are not sure why, but believe it may be that the strong dose of chemotherapy that often is part of treatment for ovarian cancer knocks out any developing breast cancers. It is always prudent for any women with a BRCA mutation to continue careful screening.
- I have BRCA1 and have melanoma. Is there a connection?
The risk for melanoma is not believed to be increased with BRCA1, only with BRCA2.
- In 1997 I had a mastectomy of one breast. I have the BRCA1 Now, at age 77 should I get a mammogram of the remaining breast?
As women age, they use up their lifetime risk for breast cancer. At a certain point, as life expectancy decreases, we stop doing this kind of screening because the risks of screening (finding something that turns out to be benign) start to outweigh the benefits. How long to continue screening is a decision to be made between a woman and her doctor. Women continue to develop breast cancer well into their 90’s; there is no age when it no longer happens.
Other Cancer Genes
- Are there any specific treatments/options for people with PALB2 mutations?
Based on national guidelines, women with hereditary PALB2 mutations should have high risk screening for breast cancer including an annual MRI beginning at age 30. They may consider the option for a prophylactic bilateral mastectomy. There is a slightly increased risk for ovarian cancer, approximately a 3-5% lifetime risk. Evidence is considered insufficient to recommend removal of the ovaries and tubes based on testing alone, but can be considered based on family history. Those with a family history of pancreatic cancer should consider pancreatic cancer screening (see question 17). A person who inherits two copies of a PALB2 mutation can develop Fanconi anemia, which can lead to birth defects and childhood cancers.
- Is it worth testing/knowing if I have CHEK2? What would change in terms of detection? One of my parents had CHEK2 and died of pancreatic cancer
I am a carrier of the CHEK2 gene; I hope to get information.
My 29 year old daughter tested positive for the CHEK2 gene (her father had breast cancer and tested positive for this gene). What other cancers are related to this gene? What is the protocol for being followed given she has this gene? Thank you
I am a breast cancer survivor and received genetic testing showing a CHEK2 mutation: variant C1283C>T. What additional risks do women with this gene mutation face?
Based on national guidelines, women with hereditary CHEK2 mutations should have high risk screening for breast cancer including an annual MRI beginning at age 40. Screening should start at a younger age if there are individuals in the family who developed breast cancer under age 50. There is not enough evidence to recommend prophylactic bilateral mastectomy, but it may be considered based on family history. CHEK2 carriers may also be at an increased risk for colon cancer and prostate cancer, but national guidelines do not have any specific guidelines as evidence is not well established. The risk for ovarian or pancreatic cancer is not increased.
There are several CHEK2 mutations that seem to have lower risk than others. One of them is C1283C>T, which is seen more commonly among Ashkenazim. You should discuss this finding with a genetic counselor.
- Is there a way to limit how Lynch Syndrome causes increased cancers?
There is Lynch Syndrome in my family history, so I am interested in hearing about this. I know so little about it, I do not know what to ask and doctors do not mention it at all unless I say something. I have spoken to the genetics counselor and donated last week.
Lynch syndrome is a result of mutations in five different genes, called MLH1, MSH2, MSH6, PMS2 and EPCAM. The cancers at highest risk to occur include colon cancer, endometrial (uterine) cancer and ovarian cancer. There may also be increased risk for urinary tract cancer, other gastrointestinal cancer including stomach or pancreas, and prostate cancer. The risks for cancer vary significantly between the genes, so it is very important to discuss the management of Lynch syndrome with a genetic counselor.
The most important thing to know about people with Lynch syndrome is that they are not more likely to develop colon polyps; however if they do develop a polyp it can change very quickly from benign to cancerous. For this reason, it is recommended that people with Lynch syndrome have a colonoscopy every one to two years.
- What do you know about Fanconi Anemia and specifically the IVS4 mutation that is prevalent in Ashkenazi Jewish women? How does that play into breast cancer?
There are approximately 10 different genes associated with Fanconi anemia. Fanconi anemia is a recessive disorder, which means you need to have two mistakes, one inherited from each parent, in order to have the disease. Some of the Fanconi genes, in the carrier state, increase breast cancer risk. I mentioned an example earlier, PALB2. The Fanconi type C gene is common in individuals with Ashkenazi ancestry, specifically a mutation called IVS4 in FANCC. There is preliminary evidence that having one mutation in this gene increases breast cancer risk, but there is not enough evidence to recommend any change in screening.
- Can you share the latest guidance for ATM carriers in terms of screening and prevention?
Based on national guidelines, women with hereditary ATM mutations should have high risk screening for breast cancer including an annual MRI beginning at age 40. Screening should start at a younger age if there are individuals in the family who developed breast cancer under age 50. There is not enough evidence to recommend prophylactic bilateral mastectomy, but it may be considered based on family history. ATM carriers may also be at an increased risk for prostate cancer, but national guidelines do not have any specific guidelines as evidence is not well established. There is a slightly increased risk for ovarian cancer, less than 3% lifetime risk. Evidence is considered insufficient to recommend removal of the ovaries and tubes based on testing alone, but can be considered based on family history. Those with a family history of pancreatic cancer should consider pancreatic cancer screening (see question 17). A person who inherits two copies of an ATM mutation can develop Ataxia Telengiectasia, which can lead to birth defects and childhood cancers.
- With my genetic testing I came back positive for the NBN gene which my surgeon had never heard of. It says it is associated with autosomal dominant predisposition to breast cancer. I was just treated for DCIS.
According to national guidelines, most individuals with an NBN mutation will not be at an increased risk for breast or ovarian cancer. There is one more common NBN mutation called 657del5 which has mixed evidence for increased risk. There is not enough evidence to recommend either breast MRI, prophylactic bilateral mastectomy, or removal of the ovaries and tubes, but these may be considered based on family history. A person who inherits two copies of an NBN mutation can develop Nijemen breakage syndrome, which is a radiation-sensitivity disorder that may result in growth retardation, immunodeficiency, and in particular, susceptibility to cancer.
Other types of Cancer
- I have 2 parents who had pancreatic cancer and I had breast cancer though we all tested negative for all genetic mutations. Does this mean I have a higher risk or not?
Interested in the BRCA2 link with pancreatic cancer as my Dad has just been diagnosed, we are awaiting treatment.
Can you recommend a research center for pancreatic cancer?
National guidelines recommend that pancreatic cancer screening be performed in experienced, high volume centers, preferably under research conditions. A list of centers can be found on the website of the National Pancreas Foundation. https://pancreasfoundation.org/npf-centers-info/pancreatic-cancer-centers/ Screening is recommended to start at age 50, unless there is a family history of pancreatic cancer diagnosed in a family member younger than age 60. Screening tests include contrast enhanced MRI/MRCP (magnetic resonance cholangiopancreatography) and or EUS (endoscopic ultrasound). Screening should only take place after an in depth discussion of the pros and cons with the experts.
- Is colon cancer related at all to breast cancer?
I’d love to hear about colon cancer risk (I`ve heard it is connected to BRCA from physicians and then that it is not connected). I also want to know what their ideal protocol is for BRCA2 patients–which checkups should we see annually, which types of doctors. My gynecologist recently asked me to get a mammogram even though I had a mastectomy. It was confusing.
Colon cancer affects approximately 1 in 18 individuals, and breast cancer 1 in 8 women, so they are both common cancers. Some families or individuals will have both kinds of cancer just by chance. There are genes that seem to increase the risk for both, like CHEK2. It doesn’t seem breast cancer risk is increased with Lynch syndrome, and it doesn’t seem colon cancer risk is increased with BRCA1 and BRCA2 mutations. However, the studies that have looked at these questions have had mixed results. It makes sense to ask your doctor, and consider screening based on the family history. As for mammograms and other imaging after mastectomy, see question 28.
- Is this BRCA test recommended for DCIS patients or survivors? If so, what determines that?
Please address how a DCIS diagnosis affects future risk.
DCIS (ductal carcinoma in situ) is a non-invasive stage zero version of breast cancer. In determining the need for hereditary genetic testing, it is considered the same as breast cancer. Those diagnosed with DCIS should be followed by their oncologist to address future risk for recurrence.
Testing, Interpretation of Testing, Retesting
- I had genetic testing a number of years ago and was BRCA positive as were many members of my family. Is there new information about the genetics that would suggest retesting periodically is valuable for more detailed genetic information?
If we had a BRCA test years ago and were negative, should I retest based on new more specific available testing?
As a 69 year old with BRCA2 mutation who has had total hysterectomy and bilateral oophorectomy is there a need to undergo further genetic testing? I have an annual diagnostic mammogram, annual breast MRI and am followed by a breast surgeon.
I was diagnosed with breast cancer 5 years ago. At the time, I tested negative for the BRCA1 and BRCA2 mutations. I have not been tested for other mutations. There is no family history of breast cancer. Should I undergo additional genetic testing?
Are those who tested positive for BRCA1 or BRCA2 likely to test positive also for these other genes?
I tested negative for BRCA1 and BRCA2 AFTER being diagnosed with triple negative breast cancer. It has been suggested that I test again but I am not inclined to do so. Neither my daughter, brother or sister want to test though I would like them to do so. I was diagnosed at 65 and am about to be 78.
What other cancers are associated with breast cancer. My dad at 92 had pancreatic cancer. I had breast cancer at 51, my daughter has breast cancer at 38. We are both BRCA negative. She had 21 genes checked. I only had the BRCA test. Should we get further testing? No one else in our family has had cancer.
I am BRCA1 positive and have had breast cancer. I have 2 daughters, one was positive, one was not. Should I be tested for other mutations? What else should my daughters be doing in terms of risk, testing, screening?
Those who have tested positively for a mutation in BRCA1 or BRCA2 generally don’t need to have additional genetic testing, unless there is a strong personal or family history of cancer that can’t be explained by the mutation identified. For those testing negative, it may be a good idea to get another test under the following circumstances: a) your original test was done before 2013, or b) your original test included only BRCA1 and BRCA2. You may consider additional testing if the original panel test you had was smaller than 10 genes, although the likelihood to find something in that case is small.
- I have a very strong family history of breast cancer. When I went for genetic testing and counseling, I was told I had no special risk for breast cancer. A few years later, I developed breast cancer at an early stage. What can we do about the breast cancer causing genes that we have not yet identified?
I`ve had genetic testing (the big one) and everything came back negative but still my sister and I both had breast cancer.
Plenty of people get breast cancer and are BRCA negative, so aren’t there probably other genetic markers they haven’t figured out yet?
I have had two breast cancers and I’ve tested negative for BRCA1 and BRCA2. My daughter is negative as is my husband. Should my other daughter be tested?
Is there a link between prostate cancer and breast cancer? My father had prostate cancer at age 62 and I have had breast cancer at age 55. I have had genetic testing with negative results for BRCA1 and BRCA2.
If someone has a strong personal and family history of cancer, and everyone in the family who has a test has negative results, the results are considered to be uninformative. This means that there may be other unidentified genes that are causing the cancer in the family. The genes that we don’t know about yet are likely to be SNPs (single nucleotide polymorphisms). These are common differences in DNA sequence between people that confer a very small increase in risk. They become clinically significant when someone carries a significant number of them. Some labs do this kind of testing, but the tests are not broadly available yet. The evidence that it is worthwhile changing care is not strong enough yet in the absence of family history.
- After being diagnosed with DCIS, I tested positive for the lynch gene. I was told in a follow up that new discoveries show that it isn’t something to worry about. Do you feel otherwise?
It sounds like you may have first been diagnosed not with a mutation, but with a variant of uncertain significance (VUS). A VUS is something different about your DNA that scientists are not sure is important or not important. Over time, labs collect evidence that leads them to change their interpretation of a VUS either to a likely positive or likely negative result.
In very rare instances, labs may change their interpretations more drastically. In this type of situation, guidance from a genetic counselor is strongly recommended.
- My daughter tested negative for BRCA2 (I am positive) but has a variant of uncertainty. She was diagnosed with melanoma age 27. Is there a connection?
When individual’s carry a variant of uncertain significance, it can be difficult to know whether those variants are significant or not. There is not enough information in this question to be able to answer it well. If you asked this question, or have a similar question, don’t hesitate to make an appointment to discuss this with me at Sharsheret.
- What’s the best way to get genetic testing since Medicare doesn’t cover it or are there labs where Medicare would cover it in NY?
There are a lot of variables involved in the ability to get a low cost test. It depends on insurance, personal and family history, and where you live. If you have questions about this, don’t hesitate to be in touch with me, or another genetic counselor. You can find a genetic counselor at https://www.nsgc.org/page/find-a-genetic-counselor.
- My father died of colon cancer. No other family members had it. Should I be tested?
You might consider genetic testing depending on his age at diagnosis. If he was over 50, and didn’t have another kind of cancer or excessive polyps, you probably don’t need a genetic test, but should see a gastroenterologist to discuss a colonoscopy.
- Why don’t we recommend BRCA1 and BRCA2 for all women? Seems a good investment. Thank you for this session.
What can a man do if he finds it difficult to get approved for genetic testing?
If your insurance will not pay for the full testing, what is the cost typically?
Do you have recommendations for where to get testing if self-pay?
Some experts do recommend screening all women or even all men and women for BRCA1 and BRCA2. This may be an especially good idea for those with Ashkenazi Jewish ancestry. If you are interested in testing even though you don’t meet your insurance company’s guidelines, tests are available for a cash price of around $250. Please be in touch with me or a genetic counselor to get guidance for a test that makes sense for you.
- My gastroenterologist recommended I have a colonoscopy every 3 years – I have the CHEK2 and on the other side of the family without the CHEK2 there’s a history of colon cancer. My oncology geneticist recommended every 5 years. I’m going with the 3 year recommendation out of abundance of caution but it seems like there’s a discrepancy in the 2 medical fields. What’s your position? Thank you.
When a genetics expert makes a recommendation for frequency of a colonoscopy, it is usually based on national guidelines in genetics. Gastroenterologists have their own set of guidelines that may be based on other criteria specific to you. For example, someone who needs a colonoscopy every 5 years may have to come back sooner once a polyp is identified. Any time there is a concerning difference in the recommendations of two different physicians, you can ask them to discuss your case with each other.
- How can a person safely have a Breast MRI during this pandemic?
How worried should breast cancer patients be about the frequency of scans (i.e., amount of radiation)?
Also, once you have an oophorectomy and mastectomy, what should your surveillance be if your doctors feel they got all the cancer and you did not need chemo or radiation? I hear conflicting information from my doctors and in doing my own research. Thank you!
Most experts recommend that individuals at high risk should continue to have their careful screening during the pandemic, whether that involves a mammogram, breast MRI, or colonoscopy. However, you should speak with your doctor to determine what makes the most sense for you.
The amount of radiation in a mammogram is very small, and does not appear to increase breast cancer risk in any significant way. Avoiding unnecessary radiation is a good idea, but mammograms are not “unnecessary”. Ultrasounds and MRIs do not have any radiation associated with them, although an MRI of the breast needs a contrast dye.
National guidelines do not recommend routine mammography, sonography or MRI after prophylactic bilateral mastectomy, as there is very little breast tissue left. There may be more indication to image women who are breast cancer survivors, but the recommendations in the medical literature and in practice are not consistent. Further study might help to clarify this issue.
- What if two parents have a mutation?
Can you have multiple mutations?
Most people who inherit two different mutations will have the risks that are associated with each mutation, but will not have any “additive or multiplicative” effect. In other words, someone with both a BRCA and Lynch syndrome mutation has the risk of each mutation, but no extra risk from the combination of both mutations.
If someone inherits the same genetic mutation on each chromosome (in other words, one mistake from each parent, not two mistakes in the gene on one side), then having no working copy from either parent may cause a more significant problem. Sometimes inheriting two copies of BRCA1 or two copies of BRCA2 can lead to Fanconi anemia. However, most of the time, and it appears almost always with the founder mutations that are common in Ashkenazi Jews, individuals who inherit two mutations, one from each parent, are never born. The embryo in this case doesn’t develop normally, and there is a miscarriage.
These issues are complicated; if you suspect this problem in your family, you should speak with a genetic counselor.
- I had a friend diagnosed with Breast CA and had a mastectomy and chemo. A number of years later she found a lump on the same side a bit higher. it was again cancerous and she had chemo and radiation. She battled 30 years which was amazing but how common is that on the same side.
Recurrences happen after a breast cancer diagnosis. The chance for a recurrence varies depending on features of each specific breast cancer. Each treatment that is done as part of the treatment is designed to reduce the risk of recurrence with the smallest amount of side effects. This process is not always successful.
- Is there any research on genetic markers for lung cancer not associated with smoking?
Yes, this kind of testing is available. You should contact a genetic counselor to find out about how to access the test.
- Which of these genes are testable before diagnosis?
Any of the genes discussed in this webinar can be tested prior to diagnosis.
- How important is it to have both oral chemotherapy and infusion therapy after chemo and radiation treatments are done?
I was diagnosed with Bladder Cancer. I didn’t have radiation or chemotherapy. The doctor gave 5 injections (they said it’s for improving the immune system). Since 2013 the doctor said I’m fine and free of cancer. Is it possible to get cancer again?
How can one avoid a recurrence of ovarian cancer?
These medical questions are important, but beyond my expertise to answer as a genetic counselor. Sharsheret does not provide medical advice. If you have reason to question the care or advice you have received from your physician, a second opinion is a good idea.
Please reach out to me any time at [email protected] or 866.474.2774 if you are looking for a more detailed explanation, or have other issues that may be more specific to your own situation.