New Tool for BRCA Women Who Face Risk-Reduction Decisions
by Margaret Snow, MD and Sue Friedman
Researcher and oncologist Allison Kurian, MD and her colleagues at Stanford University created a sophisticated computer model to estimate the survival benefits of preventative surgery compared to surveillance in BRCA carriers. The results were published in the January 10 (2010) issue of the Journal of Clinical Oncology.
Not surprisingly, combining prophylactic bilateral mastectomy and bilateral salpingooophorectomy resulted in the highest predicted overall survival for mutation carriers. Age at surgery affected survival, and some differences were identified in survival benefits of BRCA1 carriers compared to BRCA2 carriers.
Based on prior research, survival to age 70 for women without a mutation is 84% (see sidebar). BRCA1 carriers who chose no intervention have an estimated survival of 53% to age 70. Those who choose surveillance and no prophylactic surgery improved their survival to 59%. The Stanford model predicted an increase to 74% survival when these women have prophylactic bilateral salpingooophorectomy (removal of the ovaries and tubes) by age 40. Adding a bilateral mastectomy at age 40 further increased survival estimates to 77%. When bilateral mastectomy is performed at age 25, the survival estimate for this group goes up to 79%.
Women with BRCA2 are estimated to have a 71% chance of survival to age 70 without any intervention. Survival improved to 75% if they choose surveillance without surgery. Survival increased to 80% when they have prophylactic bilateral salpingo-oophorectomy by age 40. Adding a bilateral mastectomy by the same age increased survival estimates to 83%. Surprisingly, the model projected a similar survival estimate for women with a BRCA2 mutation when they have mastectomy at age 40 and delay oophorectomy to age 50.
The key finding of this study was the impact of ovarian cancer on survival and the benefit of salpingo-oophorectomy for improving survival. Compared to women who did not choose oophorectomy, a BRCA1 mutation carrier improved her survival expectancy by 15% if she had an oophorectomy by age 40. The impact of oophorectomy was a 4-6% increase in survival for women with BRCA2 mutations. The benefit was not as profound in BRCA2 mutation carriers, but it is not surprising, given their lower rates of ovarian cancer.
Dr. Kurian expressed surprise at the small difference in mortality between the breast surveillance groups compared to the preventative mastectomy groups. This is due to the study’s finding that MRI screening in combination with oophorectomy at age 40 is very effective in improving survival for BRCA mutation carriers.
Rather than following actual patients, researchers used combined data from several prior research studies to establish their model and draw conclusions. This method has its advantages, since real-time research would require many participants in each study group and might last for many years and women might not wish to participate in a randomized trial between mastectomy and breast surveillance. In the meantime, improvements in surveillance techniques and cancer treatments would continue to affect study outcomes. The Stanford model allows researchers to consider more variables and produce more results than research studies with actual patients. Using this process, researchers can account for new developments in MRI surveillance, making this research more current than some published studies with actual patients.
One thing to keep in mind about this study: researchers focused on survival from breast or ovarian cancer, rather than considering a diagnosis as an end point. For many women, the risk for developing cancer is an equally important outcome that affects their risk-management decisions. Told they are predicted to survive a cancer diagnosis, many women with BRCA mutations would prefer to do what they can to avoid cancer altogether. Models like this one help health care providers guide high-risk women in their risk-management decisions. But these models also have limitations. Risk-assessment is still not an exact science and we are still unable to express exactly what a woman’s risk for breast cancer and ovarian cancer will be in her lifetime. Individual benefits from surgical intervention may vary, limiting the predictive value of this model for any one woman.
Dr. Kurian and her colleagues are working on a followup article to provide more information about the percentage of patients experiencing cancer at different stages. Her team is also developing a program that will allow an individual BRCA mutation carrier to enter her own data to estimate differences in her projected survival based on different risk reduction choices.
The table below reports estimated survival to age 70 for several groups of simulated BRCA carriers.
Survival to Age 70
|Surveillance, no surgical intervention||59|
|Surveillance, oophorectomy at age 40||74|
|PBM at 40,* oophorectomy at age 40||77|
|PBM at 25, oophorectomy at age 40||79|
|Surveillance, no surgical intervention||75|
|Surveillance, oophorectomy at age 50||79|
|Surveillance, oophorectomy at age 40||80|
|PBM at 25, oophorectomy at age 40||83|
|PBM at 40,* oophorectomy at age 50||83|
* Includes screening with MRI/ mammogram from age 25-40
PBM = prophylactic bilateral mastectomy
Kurian AW, Sigal BM, Plevritis SK. "Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers." Journal of Clinical Oncology. January 2010; 28(2):222-231.
Stadler ZK, Kauff ND. "Weighing options for cancer risk reduction in carriers of BRCA1 and BRCA2 mutations." Journal of Clinical Oncology. January 2010;28(2):189-191.
Greenwood A. "Helping breast cancer gene mutation carriers weigh prevention choices." NCI Cancer Bulletin. January 2010;7(2).
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