BRCA Mutations and Familial Breast Cancer Risks

A study published this week in JAMA examines the risk for breast cancer in the families of women with breast cancer.

The researchers studied 2000 women with breast cancer diagnosed before age 55. Of these, about 5% of the women with unilateral breast cancer were found to have either the BRCA 1 or BRCA 2 gene mutation, while 15% of women with bilateral breast cancers were gene mutation carriers.

Overall, 75% of women with breast cancer were the only person in their immediate family to have had the disease. Among BRCA mutation carriers, 58% were the only member of the immediate family with breast cancer.

The risk for breast cancer in family members varied widely, from 30-90%, and was highest in families of women with cancers at an early age and with bilateral breast cancers.

Significant weaknesses of this study, in my opinion, were that family history of second and third degree relatives was not assessed, cancers up to age 55 (and not the usual age 50 cut off) were considered, and data on family history of ovarian cancer was not included. Family members were not assessed for the prevalence of the gene mutation, and their histories were taken second hand from the breast cancer subjects. This, the penetrance of the BRCA gene in these families was only presumed, not measured.

What To Do with this Info

The take home messages for me from this study were these –

1. BRCA testing is still uncommon, even in women who have had breast cancer. The younger your age at diagnosis, the higher the odds you will have a BRCA mutation. I believe testing is worthwhile in women who have had pre-menopausal breast cancer. But even in this group, most will test negative.

2. If your Mom or sister had breast cancer under age 55, odds are still that it was not a BRCA-related cancer. The more family members and the younger the age, the higher the risk. The best way to find out is for that person to get tested. If that person is positive, the next best step would be to get yourself tested.

But before doing this, talk to your doctor, and think hard about what you would do differently if your test was positive.

3. Even if you are a BRCA carrier, we really can’t reliably quantify your risk of breast cancer other than to say it is somewhere between 30 and 90% by age 70. That’s not very helpful, is it? The variability in risk is probably due to other genetic factors that interact with BRCA.

Family history itself may be your best indicator of your own risks. If your relative had breast cancer at a young age or had bilateral breast cancer, your risk is higher than if their cancer was at an older age and unilateral.

But how high is too high? What’s your personal risk tolerance? Does it vary with age? At what point would you take a medication (Tamoxifen or Evista) to reduce that risk? At what point would you have your ovaries removed? Not easy questions. Here’s the story of one woman who had to deal with these issues.

Myriad, the company that makes the test, has begun aggressively marketing the BRCA screening test, a step that I believe is premature. What we know about BRCA was largely learned from testing Ashkenazi Jews, a group known to be at increased risk. But we still don’t know the true prevalence or penetrance of this gene in the general population, and what it really means to be a carrier. Before we start mass screening and mass mastectomies and oophorectomies, we better know what the risks truly are for having this gene.

Studies such as this one are helpful in better defining that risk, but we have a long way to go before mainstreaming this genetic screening test.
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2 Responses to BRCA Mutations and Familial Breast Cancer Risks

  1. Ah…studies. When to live you life by them and when to just ponder the conclusions. Next month the JAMA may present a study showing a very strong familial link. Who knows.

    The fact that the research is done is fantastic – particularly for breast cancer. So much progress has been made in this field, thank goodness! However, on-going research taken as gospel is a bit freightening. How can an individual determine what to do when the medical community can’t give anything more than odds.

    At least there is a test to add to the data at hand.

    As long as the test doesn’t alone cause a patient to panic themselves into unnecessary testing, then why not know more about yourself – whether or not you are a carrier.

    If you have knowledge that you are a carrier, then more aggressive screening should be used for that patient.

    Just my $0.02.

    (please note the absense of discussion related to the pharma discussion in my post…I just don’t have it in me today! But for the sake of argument, I bet there are women out ther that are grateful that someone is talking to them, via TV ads, about the possibility of pre-screening a deadly illness…)

    Love, Scruggling.

  2. A woman I grew up with got diagnosed with breast cancer a few years ago, in her mid 20s, caught because she was having problems breast-feeding. Turned out a large number of women on one side of her family had died of breast cancer, so they did the testing, and found that both she and her younger sister had one of the mutations (I don’t remember which). So they both had some serious surgery.

    Happily, even though the odds were against the older sister, she’s still doing well now, after almost ten years. I hope by the time her daughters come of age, science folks will have come up with better alternatives. It’s pretty amazing, if you think, how fast dna knowledge is being built!

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