Home > GYN Oncology, Gynecology, Uncategorized > The Importance of Genetic Screening for Heritable Cancer Syndromes

The Importance of Genetic Screening for Heritable Cancer Syndromes


When I talk to my patients, one of the greatest concerns I hear is regarding the fear that they might get a cancer at some point in their life.  It is a very reasonable fear, as cancers of the female reproductive tract and breasts are not as rare as we might like.  Perhaps educated by Angelina Jolie’s announcement of her BRCA mutation in 2013, many women now ask me about BRCA testing.  In the past I referred to genetic counseling for this, but more recently I have become more educated on exactly who qualifies for testing, and send quite a few BRCA tests out of my office myself.

Across the board, somewhere between 1 in 8 and 1 in 10 women will get breast cancer over the course of their life, if they live to an age of 85 years old.  Fortunately cure rates are high because we have many screening methodologies that are quite effective at finding it before it has spread widely, allowing for relatively straightforward treatments that are usually curative.  These screenings include typical mammography, as well as high risk screening methodologies like breast MRI.

angelina-jolie-mastectomyOvarian cancer is far less common than breast cancer , affecting about 1 out of every 100 women, though it is also far more deadly.  While breast cancer is usually caught early enough to be cured, ovarian cancer is usually found when it is already at an advanced stage, and even with treatment significantly shortens the life of women affected by it.  We have investigated various strategies to screen for ovarian cacer, including ultrasounds and blood analyte testing (ie CA125), but to date no screening methodology has been shown to be truly useful in detecting the disease early, and unfortunately most women diagnosed eventually die from complications of the disease.

It is my impression that physician are very good at screening for breast cancer, and aware of women at high risk for ovarian cancer.   This is a good thing. What we are not  great at is identifying women who are at the highest risk of developing the disease : those that have heritable mutations such as BRCA mutation.

The most common heritable mutation for breast and ovarian cancer is BRCA 1 and 2 mutations.   BRCA 1 is present in 2-3% of the general population, in 8% of women of Ashkenazi Jewish descent, and in 4% of Hispanic women.  BRCA 2 is present in 2% of the general popuation, and in 1% of women of Ashkenazi Jewish descent, and in 3% of the African American population.

If a woman has a BRCA 1 mutation she is has a 60% chance of developing breast cancer by age 70, and a 50% chance of developing ovarian cancer.

If a woman has a BRCA 2 mutation, she has a 50 to 85% chance of developing breast cancer, and an approximately 30% chance of developing ovarian cancer.

Women that have these mutations can dramatically reduce their likelihood of dying from these cancers by doing advanced screening, and in many cases can consider removal of the potentially cancerous organs once they have completed childbearing (something brought into the mainstream awareness by Angelina Jolie a few years ago, who had a prophylactic mastectomy and oophorectomy for this reason.)

So given this important information, why are physicians not very active in ordering these tests?

The biggest reasons are two fold:  1) the tests are pretty expensive, with list prices between 2 and 4 thousand dollars depending on the lab and 2) the criteria under which these tests will be paid by insurance have been shifting in the last few years, and it has been hard to tell who will have their tests paid for and who will not.  It is not worthwhile (or cost effective) to screen every woman for BRCA, but for women of high risk is is not only useful but also cost effective.  But just how much risk is enough, and how do we quantify this and understand who will be covered for testing and who won’t?  It is this question that keeps many qualifying women from getting screened in many physician’s offices today.

Fortunately, these issues have been greatly simplified in the last two years.

In general, BRCA testing will be covered by insurance for women who meet NCCN (National Comprehensive Cancer Network) guidelines for testing, which include:

1) women who have a direct relative positive for a BRCA mutation

2) women who have breast cancer at an age less than 50

3) women who develop triple negative breast cancer at an age less than 60 (i.e. negative progesterone receptor, negative estrogen receptor, HER2 receptor negative)

4) women who have had two different breast cancers

5) women who have a first degree (ie mother / sister) who had ovarian cancer _or_ who have a second degree relative (ie grandmother / aunt ) with ovarian cancer.

6) women who have two first degree relatives with breast cancer at any age

7) women who have one relative who had breast cancer at an age less than 50

Women with family histories of pancreatic cancer may also qualify, as this disease is also associated with BRCA mutation in some cases.

For women that meet these guidelines, testing should be largely covered by insurance, and in most cases are paid entirely by insurance.  One strategy for appopriate testing is to routinely refer to genetic counseling, which if easily available will lead to the patient getting excellent information and counseling prior to having a test run, if appropriate.  This strategy works great where there is readily available appointments, and with patients that are likely to follow a doctor’s recommendation to go to such a visit.  There is, however, a subset of patients that will for whatever not reason not follow a recommendation to go to a genetic counselor.  I think in many cases the concern for a heritable cancer is something that doesn’t directly influence a patient’s life, and they put addressing in on the back burner.  As such, direct testing may lead to a greater likelihood of actually testing appropriate women, and is reasonable to consider in some practices.   In the end, I think the most important thing is that physicians keeps the issue in front-of-mind, and appropriately manage patients with a strategy that makes sense for each individual patient.

In the last few years, I have begun to test far more women than I used to.   While I have only found a single woman who actually had a BRCA mutation, I have consistently found that women who are tested and are found to be negative really appreciate having had the opportunity to be tested, and feel great reassurance that they do not have the mutation, which is of value in itself.

So if you are a physician and are not considering testing appropriate patients for BRCA, make it a more prominent part of your practice, whether that be through direct testing or routine referral to genetic counseling.   If you are a woman who has a concern about your family history of breast or ovarian cancer, please ask your doctor if its appropriate for you to be tested, either directly or through referral to a genetic counselor.  Because while screening the general population for the actual cancer is important, finding the women who are at the highest risk is also an important part of care.

Dr. Fogelson practices gynecologic surgery and general gynecology at Pearl Women’s Center in Portland, OR.   He can be reached at (503) 771-1183, or http://www.pearlwomenscenter.com./





Addenda (9/22/2016)

Not surprisingly, this post has gotten a lot of interest, mostly negatively from the genetic counseling world.   The gist is that that genetic counselors think it a terrible idea for a non-genetic counselor to order these types of tests without referring to them first, which I did suggest in the original text.

In many ways, I agree with them.   They have years of training and a deeper understanding of each potential mutation than most physicians have (absent physicians with genetics fellowships).  They also have more time to talk to patients about these issues, and thus can be more thorough in their counseling.  As such, the optimal course for patients who are considering BRCA testing, or any other genetic counseling, is to see a genetic counselor first.  Some insurers (Aetna I’m looking at you) even require it.

We must also recognize, though, that these genetic counselors see the world through a different lens than a physician that refers to them.   They see patients that come to see them and do a great job with them.  What they don’t see are the women who had discussions with their doctors about seeing genetic counselors, but that never actually came to see them.

In most cases, a concern for a heritable cancer syndrome develops because of a routine history with a thoughtful physician.   It is only the minority where a patient actually comes in with the expressed concern about a heritable cancer syndrome.   So in most cases, it is the physician who is bringing up the issue and saying “hey we should consider this issue”.  Now this consideration can be referral to a genetic counselor, or it may be considering if direct testing is appropriate.   What I know from experience, is that if I pass it off to a genetic counselor, a substantial number of patients are going to take my advice to go se them and not act on it.  After all, a genetic predisposition isn’t a sickness that a patient can feel.  If somebody has chest pain and I refer them to a cardiologist, they are going to go. But if they have a completely unseen and unfelt predisposition to some future disease, maybe they won’t.  In fact, definitely some won’t.    So the hard line everybody has to see a genetic counselor prior to testing is missing this point, in my opinion.  I think that it is entirely reasonable to ask a patient if they would like to see (or even recommend that they see) a genetic counselor, and also entirely reasonable that some patients may be tested directly.  After all, individualized care is what we do.

In the end, I think this question is a bit of a distraction, and not really the point of my article anyway.  What is important is that physicians think about this issue more.  Many physicians don’t think about it much at all, and may neither refer to a genetic counselor nor order appropriate testing.  And that is something worth trying to change.

In light of this issue, I have edited the original article a bit, as I do think it was a little too much against sending to genetic counseling, which was perhaps misguided.

  1. Rebecca
    September 6, 2016 at 3:50 pm

    Thanks for writing about this! I am someone with a strong family history of breast and ovarian cancer, and in my case it was very helpful to have my mother tested first. She turned out to be negative for all the current mutations they test for. In that case, a negative test for me would have been a false reassurance. There is something increasing risk in that branch of the family, but we can’t know if I inherited or not. So I am being more vigilant than I would have been if we believed she was BRCA positive and I came back negative. The process caused some anxiety but in the end I prefer having whatever knowledge I can get.


  2. September 6, 2016 at 4:36 pm

    Rebecca you make a great point. The optimal way to screen for BRCA is to check the person who has the disease, in this case your mother. The problem is that in some cases, that can be hard to do. In some cases the target is no longer alive, but usually the problem is just one of logistics. Inevitably what happens is that the physician refers the patient to genetic counseling and puts the burden of tracking down the right people to test to them. This is a step that will lead to some people not getting tested at all, because they never go to genetic counseling or have some significant delay in seeing them and just forget about it. So there is an optimal path and also a practical path.

    In your case, it would be interesting to have tested for the wide variety of minor breast and ovarian cancer genes that are not BRCA. Some of the lab vendors do this routinely with every BRCA test.


  3. Amy Cyr
    September 8, 2016 at 2:38 pm

    As a breast surgeon who regularly tests women for genetic causes of cancer, and who treats women with these mutations, I strongly caution against a simple increase in screening women for BRCA mutations. While it is important to identify women at high risk for developing cancer, there is potential harm that comes with genetic test results, and there is a significant amount of counseling necessary before simply sending off the bloodwork. Here is where I disagree:

    Although we are now testing more unaffected individuals, it is still ideal to test a family member with cancer as the best option. If this isn’t possible, it’s very reasonable to test unaffected patients, but you get the biggest bang for your buck by testing someone who had a malignancy.

    The problem with testing someone without cancer, when the BRCA status of the cancer-affected individuals is unknown, is that a negative BRCA test is falsely reassuring. Until you know that the cancer is the family is caused by an identifiable mutation, a negative BRCA test is meaningless. Women would still need to be treated high risk based on family history, and we do see women who don’t undergo high risk screening (such as breast MR) and who even stop getting regular mammograms because their BRCA test was negative.

    There are counseling issues regarding insurance that need to be discussed with patients. Although GINA protects again some discrimination, life and disability insurers can use genetic test results to deny policies or charge higher rates. This is some of the valuable counseling done when the patient has an hour long conversation with a genetic counselor. It’s also important to counsel women on the emotional side effects of genetic testing. What, exactly, will the woman do with that information? How will a positive result affect her? These are important parts of the counseling.

    And finally, while BRCA 1 and 2 are the most likely genetic causes of breast cancer, there are other identified genes now. Focusing on BRCA testing may leave a woman with a CDH1 or PALB2 mutation undiagnosed (and therefore leave her with a false sense of security and unscreened for other cancers). There is significant nuance to choosing which genes to test for and which company to use, Anyone ordering the testing also needs to understand variants of uncertain significance, which we are identifying with increasing frequency given the increase in panel testing. Just 2 weeks ago I saw a woman status post bilateral mastectomy and hysterectomy with BSO for a BRCA mutation. When we got a copy of her results, it was just a VUS in BRCA1. NOT a high risk gene.

    If you can’t accurately answer all of your patient’s questions about genetic testing, and if you don’t have the time to thoroughly counsel them, you shouldn’t be doing it.


    • September 8, 2016 at 5:19 pm

      Good comments there are definitely nuances to the issue. Perhaps you would like to be a guest on the Academic OB/GYN podcast to discuss the nuances of high risk screening and genetic testing?


  4. Amy Cyr
    September 9, 2016 at 1:39 am

    I’d be happy to! And I certainly don’t mean to discredit the importance of identifying high risk women. I appreciate that I am biased by seeing a lot of inappropriate genetic testing and a lot of misinformed patients, and I think testing by knowledgeable and informed providers is what we want, even if those providers aren’t genetic counselors.


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