To the Editor:

The When the Patient Asks article, “Should I be tested for the BRCA gene?” which was published in September 2009 (page 57), contains some potentially seriously misleading statements. On the Patient Information page, under the heading “What do the test results mean?” the article states:

“A negative result means that no BRCA mutation was found and that you are not at increased risk of developing any of the cancers associated with such a mutation. This does not mean that you will never develop cancer, but your risk of getting cancer is the same as that of the general population.”

A negative BRCA1 or BRCA2 test result in an individual with a personal or strong family history of breast or related cancers does not mean that the person is not at increased risk for developing any of the cancers associated with BRCA mutations, with the exception of one circumstance: the person is from a family with a known BRCA1 or BRCA2 mutation and tests negative for the familial mutation (unclear but not implied by the article). Although approximately 5% to 10% of breast cancers are the result of an inherited predisposition,1 BRCA1 and BRCA2 mutations account for only approximately 5% of breast cancers.2

Furthermore, current BRCA1 and BRCA2 testing is not able to detect mutations in 10% to 12% of families with demonstrated linkage to these genes,2 suggesting the presence of disease-causing mutations are not detectable by current analysis. Additionally, BRCA1 and BRCA2 mutations are thought to account for only about half of hereditary breast cancer;1 other as-yet-undiscovered genes are thought to account for the cancer predispositions in many of these families. Finally, there are several other genetic disorders (such as Cowden syndrome, HNPCC, Li-Fraumeni syndrome, etc.) that confer an increased risk for breast cancer; these are rarer and less well known but still must be considered in people with a personal or family history suggestive of an inherited predisposition to cancer.

It is critical that physician assistants understand that a negative test result for the BRCA1 or BRCA2 mutation in a person with a strong personal and/or family history suggestive of an inherited predisposition to cancer does not eliminate risk of such, but simply indicates that a BRCA1 or BRCA2 mutation is less likely to be the etiology in this person/family. Cancer risk in such a person or family is not the same as that of the general population; but should, in fact, be based on interpretation of the family history and consideration of genetic evaluation for other disorders associated with an increased risk for breast and related cancers. This is an excellent indication for referral to a genetic counselor and/or geneticist.

I realize most PAs don't have extensive experience with genetics—I'm one of the few dually boarded—but I'm hopeful we can increase basic genetic knowledge amongst our colleagues.

Leigh Trivino, CGC, PA-C

REFERENCES

1. National Human Genome Research Institute. Learning about breast cancer. http://www.genome.gov/10000507. Accessed October 8, 2009.

2. Petrucelli N, Daly MB, Bars Culver JO, Feldman GL. BRCA1 and BRCA2 hereditary breast/ovarian cancer. GeneReviews Web site. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=brca1, Accessed October 8, 2009.