The early discovery of the high-risk breast cancer genes BRCA 1 and 2 has made the disease a testing ground for how genetic testing can be translated into actual health benefits. The relationship between gene mutations and disease risk is not always crystal clear, but BRCA1/2 is a notable exception: women with a mutation are as much as ten times more likely to develop breast cancer. That heavy knowledge has created many ethical debates about the value of testing a patient for the risk mutations, weighing the benefits of knowing and rigorously screening versus the stress of not knowing whether any preventive measures can truly offset the genetic cancer risk.
The latter half of that equation takes a hit today with an article in the Journal of the American Medical Association that clarifies the benefits of risk-reducing surgery in patients with BRCA1 or 2 mutations. A multi-institutional study, including researchers Wendy Rubinstein and Funmi Olopade of the University of Chicago Medical Center, looked at the outcomes of thousands of women who tested positive for BRCA1/2 mutations, about half of whom chose to undergo at least one type of risk-reducing surgery. Some patients opted for masectomy, some chose risk-reducing salpingo-oophorectomy (RRSO) – the removal of the ovaries and Fallopian tubes – while others chose no surgery at all.
When researchers compared the rates of breast and ovarian cancer among the three groups, they found dramatic evidence in favor of preventive surgery. In women who underwent risk-reducing masectomy, zero percent contracted breast cancer in the following three years. Not a single case in a high-risk population, where among BRCA1/2 mutation-positive women who did not undergo masectomy breast cancer was found in 7 percent of subjects over the same three-year period.
But a masectomy is a major procedure, and despite improvements in surgical technique and cosmetic reconstruction, it carries its own substantial risk and lifestyle changes. By comparison, removing the ovaries and Fallopian tubes in an RRSO surgery is a lower risk procedure that can even be performed in outpatient settings, according to an accompanying JAMA editorial. After a mutation-carrying woman is done having children, physicians strongly recommend salpingo-oophorectomy followed by hormone replacement therapy.
The benefits of that strategy were also shown in the new paper, as RRSO decreased the risk of both ovarian and breast cancer. Again, the magic number of zero pops up in regards to cases of ovarian cancer in BRCA-2 women who underwent RRSO, while barely 1 percent of women with the BRCA-1 mutation contracted ovarian cancer after the procedure (relative to 3 percent of women without RRSO). What’s more, RRSO decreased the risk of breast cancer by two-thirds (in BRCA-2 subjects) or one-third (in BRCA-1). Those effects manifested themselves in lower mortality, which RRSO reduced by more than half in those with no prior breast cancer and 70 percent in those who had a previous cancer diagnosis.
Judging from the many news articles published immediately upon the study’s release last night, the results of the study were greeted by oncologists as much-needed proof of the effectiveness of preventive surgeries.
“We already knew intuitively that removing breasts reduces the risk of breast cancer, but this is the first paper that actually shows it contributes to a survival benefit,” said Dr. Jane Kakkis, surgical director at MemorialCare Breast Center at Orange Coast Memorial Medical Center told the Los Angeles Times. “That’s a big difference in terms of helping patients make a difficult decision.”
Now, with the amount of risk reduction firmly calculated, the critical step is making sure women found to have BRCA1/2 mutations have enough information to make that decision. Genetic counseling services become more important than ever for such cases, helping clinicians inform patients about the risks and benefits of the available options: surgery, aggressive screening, or preventive chemotherapy. The lessons learned from setting up such a process for breast cancer can set the mold for future diseases, if and when genetic risks are successfully characterized and accurate tests are constructed.