genetic codeAmong the most gratifying experiences that I have as a breast cancer surgeon is when I inform a healthy woman that she has tested “positive” for a breast cancer gene mutation.  I suspect that you have re-read the title of the blog and opening sentence a couple of time to make sure you’ve read them correctly.  Having confirmed your interpretation, you must find it quite an odd thing for me to write.   The reason that I am gratified to inform a healthy woman that she is a carrier of a breast cancer mutation is that most women are diagnosed with a mutation only after they have been diagnosed with breast or ovarian cancer.  By then, they have already lost the opportunity to do a number of key things that could have prevented them from developing cancer in the first place.

 The Negatives about “Positives”

Breast cancer gene mutations such as BRCA 1 or BRCA 2 are inheritable mutations or structural abnormalities in the genetic makeup that greatly increase a woman’s lifetime risk of developing several types of cancer.  Women testing “positive” for a BRCA 1 mutation have an 80% lifetime risk of breast cancer and a 40% lifetime risk of ovarian cancer.  Women testing “positive” for a BRCA 2 mutation have a 60% lifetime risk of breast cancer and a 25% lifetime risk of ovarian cancer.  With these kinds of statistics, you can see that testing BRCA 1 or 2 positive is a real game changer, but also a rare opportunity to positively change a person’s destiny.  By comparison, the average woman has only a 13% lifetime risk of breast cancer and a <1% lifetime risk of ovarian cancer.  Mutations of the BRCA 2 gene are also linked to an increased risk of pancreatic cancer, melanoma, and of prostate and breast cancer in men.

Like Parent, Like Child

BRCA mutations are considered autosomal dominant mutations, which means that anyone inheriting the mutations from a parent will have a high risk of developing BRCA-related cancers.  Autosomal dominant also means that all female and all male first degree relatives of a mutation carrier will have a 50:50 chance of carrying the same mutation, and of passing it on to their children.  If both parents are BRCA mutation carriers, the chance of passing on mutations to their female and male children is 100%!  Surprising to most people is the fact that BRCA mutations can be inherited equally from either the father or mother.  While the father himself might not develop breast cancer (and of course, can’t develop ovarian cancer), affected female children will be much more likely to do so.

Knowledge is Empowering

BRCA mutation-related cancers are more common than you might think.  In fact, it is estimated that 1 out of every 20 breast cancers are BRCA-related.  Even more compelling is that for every person diagnosed with a BRCA mutation, there are at least several untested and undiagnosed relatives who will remain at great risk of developing breast cancer, ovarian cancer, or one of the other BRCA-related cancers.

It should now be clear why I am so happy to find a healthy female BRCA mutation carrier.  The diagnosis of a BRCA mutation in a healthy woman is a priceless opportunity to profoundly improve the health and life of her and her immediate family.  For example, prophylactic double mastectomy or preventive removal of both breasts combined with breast reconstruction nearly eliminates the risk of developing breast cancer in a woman who would otherwise be almost destined to develop breast cancer.  Alternatively, women who may not yet desire prophylactic double mastectomy may be offered enhanced surveillance with annual mammograms and annual breast MRI to improve early detection of breast cancer.  Prophylactic removal of the ovaries after completion of childbearing will also nearly eliminate the chances of ovarian cancer.  Family members can also be counseled and tested to see if they, too, are BRCA positive.  Those testing negative for BRCA mutations can be reassured that they do not have a high risk of breast or ovarian cancer.

Slightly less gratifying, but still very pleasing, is the opportunity to diagnose a BRCA mutation in a woman who has come to me already having being diagnosed with breast cancer.  Knowledge of a BRCA mutation will enable her to consider removal of both breasts and ovaries to markedly reduce the risk of recurrent breast cancer and nearly eliminate the risk of ovarian cancer.  The family will benefit from this information as well.

Who Is At Risk

The National Comprehensive Network (NCCN) publishes guidelines outlining which women and men should consider counseling and testing for hereditary breast and ovarian cancer mutations.  In their recommendations, “Close relative” refers to 1st degree relatives (parents, siblings or children), 2nd degree relatives (aunts, uncles and grandparents), and 3rd degree relatives (1st cousins, great aunts and uncles).

For women who have already been diagnosed with breast or ovarian cancer, NCCN recommendations for BRCA gene counseling and testing include:

  • Breast cancer diagnosed at age 45 years or younger
  • Triple Negative Breast Cancer (ER-, PR-, HER2/neu-) diagnosed under age 60
  • Two Separate Breast Cancers in the same individual
  • Breast Cancer at any age with
    • One or more Close* blood relatives with breast cancer age 50 or young, or
    • One or more Close* blood relatives with ovarian cancer
    • Two or more Close* blood relatives with breast and/or pancreatic cancer at any age
    • One or more Close* male blood relatives with breast cancer

For women who have never been diagnosed with breast cancer, NCCN recommends BRCA gene counseling and testing of healthy individuals if there is a family history of any of the following:

  • Two or more breast cancers from the same side of family (maternal or paternal), including one age 50 or younger
  • One or more ovarian cancers
  • Combination of breast cancer with one or more of the following cancers: thyroid, melanoma, sarcoma, endometrial, pancreatic, or stomach cancer.
  • Two separate breast cancers in the same individual
  • A known mutation in a breast cancer gene
  • Ashkenazi Jewish descent with breast cancer at any age
  • Close male relative with Breast Cancer

Getting the Answer

BRCA testing may be performed using a simple blood or oral test called BRCAnalysis®, the only FDA approved test for looking for BRCA1 and BRCA2 gene mutations.  The test typically takes 2-3 weeks to process and is covered by most health plans ($4,500).  Uninsured women qualify for testing if diagnosed with breast or ovarian cancer.  Unfortunately, uninsured healthy women find it much harder to get tested.  “Positive” test results means that a mutation has been identified and that the person is at high risk of BRCA-related cancers.  “Negative” results mean that there is no increased risk of BRCA-related cancers.

Many women and men are often concerned about the health insurance and employment implications of a “positive” test result.  They should feel reassured that federal law prohibits health & life insurance companies and employers from discriminating on the basis of BRCA test results.

Families are Like Potato Plants…

The best parts are underground!  It’s surprising how little most people know about their family’s health history.  Yet, the cancer history of a family is vital to understanding an individual’s own cancer risk.  Unfortunately, most people learn their family’s cancer history only after they or another close relative has been diagnosed with cancer.  To see if you should consider BRCA gene testing, begin by talking to your close relatives to find out which cancers have appeared in your family.  If you find cancer patterns that suggest a BRCA-gene mutation, contact your doctor  to inquire about hereditary breast and ovarian cancer genetic testing.  Now’s the time to get digging.