Prophylactic Mastectomy and the Breast Cancer Genes
A study published in the New England Journal of Medicine (NEJM) has concluded that prophylactic bilateral mastectomy can significantly reduce the risk of breast cancer in women who carry the BRCA1 or BRCA2 gene mutations.
Prophylactic ("preventive") mastectomy involves the removal of one or both healthy breasts when there is no sign of cancer. The procedure is a major operation that is usually followed by immediate (simultaneous) breast reconstruction. It is a drastic alternative undertaken by women who consider themselves to be at very high risk for the disease.
In 1994, researchers from the National Institutes of Health were studying three families of Ashkenazi Jews that had an extremely strong history of breast cancer. The families were not known to be related, but they each carried an identical defect (mutation) on a specific gene that the researchers called BRCA1 (BReast CAncer 1). Every person carries this gene, but most do not have the mutated version.
In recent years, scientists have identified an additional gene-BRCA2-which, along with BRCA1, seems to account for the majority of inherited cases of breast cancer. However, only five to ten percent of breast cancer cases are caused by this type of inherited, genetic defect.
The NEJM study involved 139 women with BRCA1 or BRCA2 mutations who were considered at very high risk for developing breast cancer. Seventy-six of the women underwent prophylactic mastectomy while 63 opted for "surveillance" with intensive screening.
Over the three-year study period, none of the women in the prophylactic mastectomy group developed breast cancer, while 8 of the 63 women in the surveillance group eventually developed the disease.
The researchers, led by Dr. Jan Klijn of Erasmus University Medical Center in Rotterdam, concluded that prophylactic mastectomy is clearly an effective procedure for the small percentage of women who are at high risk for the disease based on BRCA1 and BRCA2 gene mutations.
However, they cautioned that more studies need to be done to determine the longer-term impact of the procedure, especially beyond the three-year follow-up involved in their study. "Longer follow-up and studies of more patients are required to establish the protective effect and determine the long-term complications of this procedure," they wrote.
In an accompanying editorial, Dr. Andrea Eisen of McMaster University in Ontario and Dr. Barbara Weber of the University of Pennsylvania noted that prophylactic mastectomy is "clearly the right choice for some women." But they added that for many others, "oophorectomy and tamoxifen in conjunction with intensive screening that includes magnetic resonance imaging is a viable alternative."
While prophylactic bilateral mastectomy appears to be effective, it remains extremely controversial. Women who are at high risk and considering the procedure are usually given at least two other options: very careful monitoring (which most women choose), and "chemoprevention" with tamoxifen.
It is important to keep in mind that if breast cancer is caught early, it is highly curable. Careful monitoring, therefore, is often an acceptable alternative.
SOURCE:
New England Journal of Medicine, July 19, 2001; 345:159-164, 207-208
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