Research Review

 

Prophylactic Mastectomy and Genetic Risk

A report just published in the Journal of the American Medical Association found that a majority of women are satisfied with their decision to have undergone bilateral prophylactic mastectomy due to their high risk for breast cancer. Prophylactic mastectomy involves the removal of one or both (bilateral) breasts when there is no clinical sign of cancer. It is a drastic alternative undertaken by women who consider themselves to be at extremely high risk for the disease.

Dr. Marlene Frost and colleagues from the Mayo Foundation and Clinic in Rochester, Minnesota, interviewed 572 women with a family history of breast cancer who had a bilateral prophylactic mastectomy between 1960 and 1993. They found that 70 percent of the women are satisfied with their decision and almost all of them (two-thirds) would "definitely" or "probably" choose to have the procedure again. Furthermore, 74 percent of the women said they are now less concerned about developing breast cancer.

Last year Mayo Clinic researchers reported that prophylactic bilateral mastectomy reduces the risk of breast cancer by about 90 percent in women at high risk due to a family history of breast cancer. And at the recent annual meeting of the American Association for Cancer Research, Mayo's Dr. Lynn Hartmann further reported that women at genetic risk who carry the BRCA1 and BRCA2 gene mutations also have a 90 percent risk reduction after this procedure. "Prophylactic mastectomy appears to reduce the risk of breast cancer in mutation carriers to the same degree that it does in women who are considered high risk on the basis of family history alone," Hartmann said.

While prophylactic bilateral mastectomy appears to be effective, it remains extremely controversial. The procedure involves major surgery and is usually followed by breast reconstruction. Women who are high risk and are considering the procedure are usually given at least two other options: very careful monitoring (which most women choose), and chemoprevention with tamoxifen.

A separate study led by Dr. Timothy Rebbeck of the University of Pennsylvania found that women with BRCA1 gene mutations can cut their risk of developing breast cancer by as much as 72 percent by undergoing bilateral prophylactic oophorectomy, which involves the surgical removal of the ovaries.

Writing in the Journal of the National Cancer Institute, Rebbeck cautioned that the potential benefits of the procedure must be weighed against the "primary negative side effect of surgery-the induction of premature menopause-which increases a woman's risk of osteoporosis and heart disease." However, an accompanying editorial by Dr. Kathy Helzlsouer of the Johns Hopkins School of Public Health noted that women who subsequently used hormone replacement therapy were able to counteract these risks while still obtaining the benefits that ovary removal had for breast cancer.

Should You Be Tested?

With respect to breast cancer, it is important to note that BRCA1 and BRCA2 gene mutations are only associated with hereditary forms of the disease-and only about 5 percent of all breast cancers are inherited. The remaining 95 percent are non-hereditary or of unknown cause.

Both men and women can inherit and pass on defective BRCA genes. Families in which breast cancer is inherited typically demonstrate the following characteristics:

However, breast cancer is common enough that random, non-inherited breast tumors may appear in more than one member of a single family. But even that does not mean family members have inherited an abnormal gene which predisposes them to breast cancer, especially if the disease occurs late in life.

Genetic Testing

Even if a woman has a family history of breast cancer, or is associated with a higher-risk ethnic population, the value of genetic testing remains highly controversial. Studies show that when women are asked what they would do in the hypothetical situation of learning that they express high-risk breast cancer genes, the overwhelming majority say they would decline prophylactic mastectomy. Instead they would opt for increased screening and surveillance.

For women confronted with being at high risk of developing breast cancer, they have several options for breast cancer prevention: close surveillance by health care professionals skilled and experienced with this type of monitoring of women at risk; chemoprevention with tamoxifen; or prophylactic mastectomy. Other research studies being developed also look at potentially other options in the future to also consider.

At a recent Gene Media Forum sponsored by Syracuse University, Dr. Neil Holtzman of Johns Hopkins Medical Center in Baltimore asked rhetorically: "[If a woman went for testing and] had a positive test result, what should she do? If she gets a bilateral prophylactic mastectomy will she do better, or will she do just as well with more frequent monitoring? The answer is we don't know." He added that if a patient's family history has already caused her to seek maximum surveillance, a positive test result might have no effect on her behavior or that of her physician.

And not only would a positive genetic test be of concern to the individual, but it would also have implications for other family members. Should sisters be tested? How will they cope? Should daughters be tested? And at what age?

Privacy Issues

Furthermore, how private would information from genetic testing be? According to a disturbing study presented at a meeting of the Society of Human Genetics conference, a majority of genetic counselors would pursue genetic testing for themselves but would keep test results off their medical records.

Ellen Matoloff of the Yale Cancer Center in New Haven, Connecticut and colleagues from the Yale University School of Medicine surveyed 296 genetic counselors belonging to the National Society of Genetic Counselors to determine their fears of genetic discrimination. The majority said they would pursue testing for hereditary genes if they had a 50 percent chance of being carriers. But two-thirds of them said they would not bill their health insurance company for such testing, and one-quarter of them said they would use an alias.

Coping with Risk

Nonetheless, experts almost universally agree on the importance of genetic counseling once a genetic marker for cancer has been identified. There are often many complex psychosocial and economic issues that a patient must suddenly cope with. And the resultant emotional burden may actually overwhelm the genetic risk itself.

SOURCES:


Journal of the American Medical Association, July 19, 2000; 284: 319-324
The Mayo Clinic (www.mayo.edu)
Abstracts from the Society of Human Genetics Conference, October 22, 1999
Abstracts from the annual meeting of the American Association of Cancer Research, April 4, 2000
Journal of the National Cancer Institute, Sept. 1, 1999; 1442-1443, 1475-1479

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