STUDY GAUGES BENEFITS OF MASTECTOMIES.

Byline: Richard Saltus The Boston Globe

Women who choose the drastic step of having their breasts surgically removed because they harbor inherited breast cancer genes could gain an average of three to five years of life, a new study concludes.

The study is the first to estimate how much time a prophylactic mastectomy would buy for a woman with a sharply increased risk of breast cancer.

The study is one of four published today in the New England Journal of Medicine that reveals new findings about the threat posed by two inherited genes for breast and ovarian cancer, called BRCA1 and BRCA2.

Until recently, there has been little scientific guidance for women agonizing over whether to have their breasts or ovaries removed because they carry a mutant gene. It seemed logical the radical step would reduce the risk, but mastectomies inevitably leave behind some breast tissue - enough to potentially spawn a tumor.

Earlier this month, Mayo Clinic researchers said the surgery could reduce the breast cancer risk by 91 percent. But they didn't quantify the benefit in added years of life.

In the study from Boston's Dana-Farber Cancer Institute, Drs. Deborah Schrag and Jane Weeks made calculations assuming that a prophylactic mastectomy would cut cancer risk by 85 percent. They found that a woman having the operation at age 30 would gain up to 5.3 years of life: The exact payoff depends on how much the mutant gene raises her risk of cancer, and that is still uncertain. Waiting until age 40 for surgery reduces the gain to 3.6 years, and by age 60 it would be less than a year.

Similarly, an oophorectomy to remove the ovaries at age 30 would yield up to 20 months of life, said Schrag and Weeks.

``We want to make it clear that we are not advocating these procedures,'' said Schrag in a telephone interview. ``But women are being tested now'' for the breast cancer genes, ``and we want to make the best data available to them.'' She said she knows of only about 10 Boston-area women who have chosen to have their breasts removed since testing became widely available less than two years ago.

In a second study, government researchers found that the BRCA1 and BRCA2 genes raise the risk of breast and ovarian cancer less than earlier estimates. A woman with a BRCA1 or BRCA2 gene has about a 56 percent risk of developing breast cancer by age 70 - compared with the usual risk of 12 percent - and a 16 percent risk of ovarian cancer.

Earlier estimates had been that either mutation raised the chance of getting breast cancer by age 70 to a terrifying 87 percent. The new estimates are for women without a particularly strong family history of breast cancer.

The figures are based on a study of 5,300 blood samples given by Ashkenazi Jewish volunteers in Washington, D.C. Ashkenazi women, whose forbears came from central Europe, have a high rate of mutant BRCA1 and BRCA2 genes - over 2 percent - and the mutations are relatively easy to detect.

``It's still a pretty impressive risk, but qualitatively different from 87 percent,'' said Dr. Jeffery Struewing of the National Cancer Institute. He emphasized that 56 percent is an average that includes women from high-risk families as well as those with few cases in their family background. The risk for any one individual is hard to estimate, he said.

In another study, Dr. Barbara Weber and colleagues at the University of Pennsylvania School of Medicine reported that most women who seek testing at a breast cancer clinic will be found not to have BRCA1 mutations. Among women who sought testing because they had breast cancer and a family history of breast or ovarian cancer, only 16 percent had a mutant BRCA1 gene. Earlier studies had suggested that 45 percent of all hereditary breast cancer was due to a BRCA1 mutation.

Dr. Thomas Frank, medical director of Myriad Genetics, a Salt Lake City company that sells the gene tests, said data he will present at a meeting next week may help clarify which women would get meaningful results from testing. The BRCA1 gene ``is not as important as we thought in women with just breast cancer'' in their families, he said.

In the fourth study, Dr. Daniel Haber and colleagues at Massachusetts General Hospital report that BRCA2 mutations seem to cause fewer cases of breast cancer in young women than BRCA1 mutations do. At older ages, both mutations have similar impact, the team found.

``Our results show just how complicated it can be to interpret the results of testing for mutations in these genes,'' said Haber, director of the MGH Center for Cancer Risk Analysis. The same gene may causes risks that are ``quite different for women at different ages.''