By Frances Bishopp

The results of the largest study to date of breast and ovarian cancer diagnosis and the presence of BRCA1 genetic mutations has demonstrated approximately one in six women who contracted breast cancer before the age of 40 carry a mutation and the presence of ovarian cancer in the family greatly increases the likelihood of having a BRCA1 mutation.

The recently concluded study was conducted by researchers at Myriad Genetics Inc., in collaboration with 21 institutions worldwide, and involved 830 participants with breast cancer, ovarian cancer or both.

The purpose of the study, William Hockett, director of corporate communications at Myriad, told BioWorld Today, was to provide data on the prevalence of one of the breast cancer genes among women with breast or ovarian cancer and the extent to which age of diagnosis and family history raises a woman's chance of carrying a mutation.

The study, Hockett said, may help to define which women would benefit most from BRCA1 testing.

All of the testing was done in Myriad laboratories, Hockett said.

The study analyzed data from sequencing the BRCA1 gene (more than 5,500 chemical "letters") in all of the women and compared the results to family history and age of onset. Overall, 170 women in the study (20 percent) were found to carry abnormalities in the BRCA1, gene of which 118 mutations (14 percent of the total, or 69 percent of those with any mutations) were known to contribute to the development of cancer.

A woman with breast cancer by age 50 and no other relatives with breast or ovarian cancer was found to have a one in 15 chance of carrying a BRCA1 mutation. If that woman has a single relative with ovarian cancer, however, the risk jumps to one in three.

Even families without many breast cancers were found to be at increased risk of having a BRCA1 mutation if there was any history of ovarian cancer, and if any of the breast cancers occurred at or before the age of 50.

The study also demonstrated that families in which there are two women with early-onset breast cancer are at increased risk of possessing a BRCA1 abnormality.

Also, a deleterious mutation of BRCA1 was found in 15 percent (six of 40) of families of Ashkenazic ancestry (central or Eastern European Jews) with at least one woman with breast cancer under age 50 but no relatives with ovarian cancer. The mutation also was found in 64 percent (18 of 28) of Ashkenazic families with just one woman with breast cancer under age 50 and at least one relative with ovarian cancer.

"Ovarian cancer in the family history has proved to be more important than we originally thought," Hockett said. "If a woman had one family member with it, she would have a 30 percent chance of having a mutation in the BRCA1 gene. Mutation raises your risk of ovarian and breast cancer somewhere between 50 and 85 percent, depending on the group you are in."

Myriad Genetics, of Salt Lake City, led the scientific teams that discovered the complete sequence of both the BRCA1 and BRCA2 breast cancer genes, and in October 1996 introduced its first genetic test, BRCAnalysis, to the market. The BRCAnalysis is presented in the form of a laboratory service and can be bought from Myriad for $2,400.

BRCA1 is one of two genes responsible for most inherited forms of breast cancer (the other is BRCA2). Although a mutation in BRCA1 is relatively uncommon among the general population, accounting for about 5 percent of breast cancer diagnoses, an estimated 1 million women in the U.S. and Europe carry mutations.

Women who carry a mutation in BRCA1 have a greatly increased risk of developing breast and ovarian cancer during their lifetimes. Among women who have already had breast cancer, those carrying a predisposing mutation are more likely to experience a second breast cancer or ovarian cancer.

For woman in the study who found they have the mutation, Hockett said, they and their doctors will decide what the next step will be. Regular mammograms and even preventive surgery have proven effective, as well as various regimens of drug therapy. *