When two genetic testing companies - OncorMed Inc. (ONM, Gaithersburg, Md.) and Myriad Genetics Inc. (MYGN, Salt Lake City, Utah) - launched comprehensive BRCA1 and BRCA2 gene sequence analysis tests to identify hereditary mutations for breast and ovarian cancer, one might have imagined a collective thanks heard round the nation. Instead, the availability of the tests - ONM's in 1995 and MYGN's in 1996 - has rekindled debate on the pros and cons of genetic testing.

Among viewpoints shared with BioCentury, there was agreement that the attention focused on the launch of the BRCA tests is typical of new technology that hits the market requiring a lot of explanation. "This test is the pioneer," said Amy Langer, executive director of the National Alliance of Breast Cancer Organizations (NABCO), "and will have to prove itself in the face of our not yet having any idea what the real demand for it will be."

Although there is growing evidence that the tests will be relevant to non-hereditary cancers, the services now are targeted at only 5-10 percent of the 185,000 breast cancer diagnoses expected in the U.S. in 1997. But they have acted as lightning rods for the larger debate on genetic testing and related privacy issues - including the media attention to some half dozen genetic privacy bills introduced in Congress in the last session.

Among the specific criticisms being leveled at the BRCA tests: their market launch occurred before there was enough clinical data to address accuracy, interpretation and efficacy questions; the lack of FDA regulation means the tests don't have to prove "clinical validity"; and no one is yet certain who will qualify for insurance coverage, and on what basis.

The backdrop

The BRCA gene is a tumor suppressor. When BRCA1 is abnormal, the resulting protein is also abnormal. Depending on the type of mutation, the protein may be unable to perform its function adequately to suppress tumor formation. About 10 percent of all cases of breast cancer - and a somewhat smaller percentage of ovarian cancer- are considered to be due to a genetic mutation.

Persons with a BRCA1 mutation have up to an 86 percent risk of developing breast cancer and up to a 44 percent risk of developing ovarian cancer by age 70, compared to risks of 10 percent and 1 percent, respectively, in the general female population. In the Ashkenazi Jewish population, a single BRCA1 mutation called 185delAG is commonly seen in families with breast and ovarian cancer. About 1 percent of Ashkenazi Jews carry the mutation, leading to estimates that it accounts for some 20 percent of cases of breast cancer and 39 percent of ovarian cancer diagnosed in Jewish women under the age of 50.