Mayo Clinic Study Demonstrates Effective Preventive Option for Women with Genetic Predisposition to Breast Cancer

Wednesday, March 29, 2000

ROCHESTER, MINN. — New results from an ongoing Mayo Clinic study show that there is an effective preventive option for women who have a genetic predisposition to breast cancer: prophylactic mastectomy, or surgery that removes the breasts as a preventive measure before the appearance of cancer. These new findings will be presented Monday, April 3, by Lynn Hartmann, M.D., a Mayo Clinic oncologist and principal investigator of the study, at the American Association for Cancer Research annual meeting in San Francisco, Calif. "We have known that prophylactic mastectomy reduces the risk of breast cancer by approximately 90 percent for women at risk for breast cancer due to family history," says Dr. Hartmann. "We haven't known until now if it would be as effective for women who actually carried mutations in BRCA1 and BRCA2, genes that normally regulate cell growth and division. These new results show this surgery also reduces the risk by approximately 90 percent in mutation carriers." This new information allows women who test positively for BRCA1 or BRCA2 and their physicians to make more informed decisions as they assess options for preventing the onset of breast cancer. Other alternatives available include tamoxifen and close surveillance, each of which has pros and cons, according to study authors. The authors also point out that the choice to undergo a prophylactic mastectomy remains in the hands of the individual patient.

"The decision to proceed with prophylactic mastectomy is a very complex and personal one," says Dr. Hartmann. "While physicians can provide long-term data, both positive and negative, regarding all the available options, the final decision to undergo the procedure remains with the patient." "As a research community, we continue to search for medical options that would be equally effective for preventing breast cancer," says Dr. Hartmann. Breast cancer affects one in nine women in the United States during their lifetimes, and five percent to 10 percent of breast cancers occur in women with an inherited risk for the disease. Women who have inherited mutations in BRCA1 or BRCA2 have a high lifetime risk of breast cancer, ranging from 56 to 85 percent.

There are still some important unknowns in genetic predisposition to breast cancer, however. Researchers believe there may also be a BRCA3, which has not yet been identified, as well as other yet unknown genes that predispose to breast cancer.

The Study: A Summary

In the previously reported Mayo Clinic study, published in the Jan. 14, 1999, edition of New England Journal of Medicine, researchers conducted a retrospective study of 639 women with a family history of breast cancer who had prophylactic mastectomy at Mayo Clinic between 1960 and 1993. The women were divided into two groups according to their assessed levels of risk for breast cancer. Researchers identified 214 women who were at high risk and 425 who had moderate risk for the disease, based on family history. These women were studied and followed to determine how many went on to develop breast cancer despite having a prophylactic mastectomy. There was an approximate 90 percent reduction in occurrence of breast cancer in the 639 women overall. Deaths from breast cancer also were reduced significantly. In the latest study, the investigators completed BRCA1 and BRCA2 mutation screening for 148 families from the high-risk group. The researchers began the blood testing with the closest, youngest living relative affected with breast cancer. If an alteration was found in that relative, the investigators searched for the same alteration in the woman who had bilateral prophylactic mastectomy. Mutations in BRCA1 or BRCA2 were found in 28 of the women who had undergone the prophylactic surgery. Of these, 17 have known deleterious, or demonstrated to be disease-causing, mutations. Mutations of unknown clinical significance, or alterations for which the scientific literature cannot yet confirm relationship to breast cancer, were found in 11 women. The 28 women were followed for a median of 15.5 years since prophylactic mastectomy, and none have developed breast cancer. ### Lisa Copeland

at Mayo Clinic (through March 30) 507-538-0844 (days) 507-284-2511 (evenings) e-mail: newsbureau@mayo.edu

at AACR (March 31-April 4): 507-261-0516

###

To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com is available as a resource for your health stories.