Prophylactic Oophorectomy Reduces Breast Cancer Risk in BRCA1 Carriers
November 1, 1999 4 minutes read
Prophylactic Oophorectomy Reduces Breast Cancer Risk in BRCA1 Carriers
Abstracts & commentary
Synopsis: BRCA1 mutations are now recognized to confer an increased risk for both ovarian and breast cancer in women who are carriers. Some women at increased risk have elected to have either oophorectomy (to prevent ovarian cancer) or bilateral mastectomy (to prevent breast cancer). The purpose of the current research was to address whether oophorectomy would afford protection from breast cancer in BRCA1 carriers.
Sources: Rebbeck TR, et al. J Natl Cancer Inst 1999; 91:1475-1479. Helzlsower KJ. J Natl Cancer Inst 1999; 91:1442-1443.
Since the initial identification and cloning of the BRCA1 gene earlier this decade, there has been a rapid application of genetic screening for mutations in this gene because of the demonstrated inheritability of the mutated variants and the increased susceptibility to both ovarian and breast cancer recognized in carriers.1 Women confronted with the knowledge that they are carriers have been faced with options that include oophorectomy (to prevent ovarian cancer) and/or mastectomy (to prevent breast cancer).
However, oophorectomy is an effective endocrine treatment for breast cancer and it is conceivable that an alteration in the hormonal milieu might influence the development of breast cancer in women at risk. The purpose of the current study was to determine if prophylactic oophorectomy conferred any benefit with regard to breast cancer development in BRCA1 carriers.
Women from five North American centers (Creighton University, Dana-Farber Cancer Institute, Fox Chase Cancer Center, University of Pennsylvania, and the University of Utah) with disease-associated BRCA1 mutations were examined with regard to breast cancer development. A cohort of these women (n = 43) had previous oophorectomy to prevent ovarian cancer. These individuals were matched (by age and participating center) with controls, who were women (n = 79) with similar BRCA1 mutations but no prior oophorectomy. As many controls as possible were studied, but each subject had at least one matched control. None of the subjects or controls had prior breast or ovarian cancer.
Approximately one third of the women in the overall series developed breast cancer (38% of the nonsurgical controls and 23% of those who had prophylactic oophorectomy). Analysis of the data indicated a significant reduction in breast cancer after surgery, with an adjusted hazard ratio of 0.53 (95% CI = 0.33-0.84). The protection was greatest for women who were followed for 10 years or longer after oophorectomy. Interestingly, the use of hormonal replacement therapy did not negate the reduction in breast cancer risk after surgery.
Thus, Rebbeck and colleagues conclude that bilateral prophylactic oophorectomy reduces breast cancer risk as well as ovarian cancer risk and should be considered when thinking about cancer prevention strategies in BRCA1 mutation carriers.
COMMENTARY
Helzlsower, in her commentary on this research, remarks on the frustrations that have occurred with the widespread genetic screening for BRCA1 in patients with strong family histories for breast cancer. The techniques involved in identifying high-risk individuals were developed and applied before effective prevention strategies were in place. Thus, there are now large numbers of women who know they have exceedingly high risks for breast or ovarian cancers, but the question remains—what to do?
Certainly, prophylactic oophorectomy and mastectomy are options but are such invasive procedures, with their inherent infringement on quality of life, required? The current study provides some good news for those who had elected to have their ovaries removed. It is clear that their risk for breast cancer is reduced but not eliminated.
The development of breast cancer in 23% of the group that had oophorectomy indicates that the risk still exceeds that of the general population (i.e., women without BRCA1 mutations). The magnitude of the reduced risk is comparable to that obtained from prophylactic tamoxifen in women at increased risk of breast cancer.
What is interesting about the report is what it tells us about the biology of breast cancer. It is probable that the mechanism accounting for reduced breast cancer after oophorectomy relates to ovarian endocrine ablation. Thus, it is surprising that women who were placed on hormone replacement therapy (HRT) after oophorectomy also were at lower risk than controls. However, there was incomplete data with regard to the duration and type of hormonal replacement in this report to be confident that this will remain the case when a larger sample is examined.
The protection conferred by oophorectomy in this special population would suggest that those BRCA1 carriers participating in the tamoxifen and raloxifene studies may also be shown to benefit from these interventions, at least with regard to breast cancer development. However, these individuals may remain at increased risk for ovarian cancer.
Thus, the data are encouraging, primarily because they indicate that risks for breast cancer in this population might well be reduced by interventions that fall short of bilateral mastectomy.
Oophorectomy, or possibly medications such as tamoxifen or raloxifene may provide sufficient risk reduction to allow at least half of these women to be spared the development of breast cancer. However, further research is necessary to develop more effective approaches, with a particular emphasis on maintaining quality of life.
Reference
1. Miki Y, et al. Science 1994;266:66-71.
Which of the following statements about the effect of prophylactic oophorectomy on the development of breast cancer in BRCA1 carriers is true?
a. Prophylactic oophorectomy eliminates the risk for both ovarian and breast cancer.
b. Prophylactic oophorectomy reduces the risk of both ovarian and breast cancer.
c. Prophylactic oophorectomy reduces the risk of ovarian cancer but increases the risk of breast cancer.
d. Prophylactic oophorectomy eliminates the risk of ovarian cancer but has no effect on the development of breast cancer.
e. Prophylactic oophorectomy has minimal effect on the risk of both ovarian and breast cancer.
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