Studies may have exaggerated cancer risk from breast cancer gene mutations

Wednesday, August 21st 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ Some women with gene mutations have had their breasts removed after studies showed they were at a high risk of cancer. A new analysis suggests the studies may have exaggerated the breast cancer risk.

Precautionary breast removal, called prophylactic mastectomy, has been performed for many women who have a high frequency of breast cancer in their families and who have mutations in the BRCA1 and BRCA2 genes. Such women are thought to have lifetime breast cancer risks of 80 percent or more.

But Colin B. Begg of Memorial Sloan-Kettering Cancer Center in New York said this high risk rate cannot be applied to every woman with mutations of the BRCA genes.

``It is likely that the typical mutation carrier would have risks lower than that,'' said Begg, who wrote an analysis published this week in the Journal of the National Cancer Institute. ``Relatively few mutation carriers would have risks that high.''

Some experts acknowledge there probably have been women who chose to have their breasts removed based on data now known to be exaggerated.

Begg said early studies that evaluated breast cancer risk among gene mutation carriers selected women in families where sisters, mothers and grandmothers had breast cancer. This created a statistical bias that skewed risk estimates for women in the general population, he said.

``The risks that have been quoted are among the highest because they have been based on studies using high-risk families,'' Begg said in a telephone interview from France, where he was on vacation.

Later studies showed the breast cancer risk among mutation carriers ``is highly variable,'' he said. ``The average risks are lower than what has been quoted.''

``We don't know at the moment how to predict risks well for the individual,'' he said.

Dr. Kathy J. Helzlsouer, an epidemiology professor and medical oncologist at Johns Hopkins University in Baltimore, said she and most other doctors and genetic counselors have realized in recent years that a lot of uncertainty remains in computing cancer risks among women with the BRCA gene mutations.

Yet some women probably chose to have their breasts removed based on exaggerated data ``because that is all we had.''

``We've all been concerned about the numbers,'' Helzlsouer said. ``Big decisions are being made based on the estimates of risk, so we need to keep doing research on it.''

Helzlsouer said medical counselors face the challenge of advising patients on what option to follow if they discover they have a BRCA gene mutation. Some may choose a mastectomy, while others may decide to take medicine, such as tamoxifen, to lower the risk. Still others may decide to do nothing.

``If you say to everybody who comes in with the mutation that their breast cancer risk is up to 75 to 80 percent (based on the early studies), we know that is way too high,'' said Helzlsouer. ``So what is the real risk (for the individual woman)? The answer is, we don't know.''

But clearly women with BRCA gene mutations have a breast cancer risk much higher than the lifetime risk of 11 percent to 12 percent for the general female population in the United States, said Helzlsouer. She said a study of mutation carriers in Iceland found a 20 percent risk, while a similar study among Ashkenazi Jews found a 56 percent lifetime risk.

``Some women will look at that and say, `Well, since it's about 50-50, I will try other means and not remove parts of my body,''' said Helzlsouer. ``But others will say, `That's too high for me' and choose mastectomy.''

Both Begg and Helzlsouer see an urgent need to determine precisely the breast cancer risk for women with specific types of BRCA mutations. There is a genetic revolution under way in medicine and many experts believe genetic profiles of patients will eventually become routine.

Begg said when it becomes common to identify women whose only breast cancer risk factor is gene mutation, ``We need to know how to advise them.''