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BRCA status predicted risk-reducing salpingo-oophorectomy
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Negative BRCA status was associated with a decreased likelihood of ovarian cancer risk-reduction strategies, although many non-BRCA carriers still underwent these interventions, according to study results.
The researchers attempted to provide further data on ovarian cancer screening and risk reduction behaviors among women without a BRCA mutation.
The investigators analyzed data on 1,447 women who were followed for a median of 3.7 years after BRCA testing. Women had received genetic counseling in addition to the test. The response rate was 77.6%, for a final cohort of 1,077 respondents.
The researchers hoped to find prognostic factors for risk-reducing salpingo-oophorectomy, screening transvaginal ultrasonography and screening serum cancer antigen 125.
The investigators reported positive results for a deleterious mutation in 18.7% of respondents. True negative results occurred in 9.6% of the cohort, and 71.8% received uninformative results. Risk-reducing salpingo-oophorectomy was performed in 19.1% of eligible women, while 39.6% underwent screening procedures.
Positive BRCA status was a predictor for risk-reducing salpingo-oophorectomy (OR=28.1; 95% CI, 16.2-48.6), transvaginal ultrasonography (OR=9.5; 95% CI, 4.3-21.0) and serum cancer antigen-25 (OR=13.0; 95% CI, 5.5-29.0).
True negative BRCA status was associated with a reduction in the likelihood of risk-reducing salpingo-oophorectomy (OR=0.1; 95% CI, 0.0-0.6), transvaginal ultrasonography (OR=0.2; 95%, 0.1-0.5) and serum cancer antigen-125 (OR=0.3; 95% CI, 0.1-0.7).
Among women in the subset who received uninformative BRCA test results, 12.3% subsequently underwent salpingo-oophorectomy, 33.8% reported undergoing screening serum cancer antigen-125 after their test and 37.3% reported undergoing screening transvaginal ultrasonography following BRCA testing.
The researchers also compared screening rates in the preceding 3 years on the basis of BRCA results, They determined that 69.6% of BRCA carriers, 30.2% of women with uninformative results and 9.6% of women with true-negative BRCA results reported having undergone ovarian cancer screening.
“Results of BRCA testing strongly predict [risk-reducing salpingo-oophorectomy] and ovarian cancer screening,” the researchers wrote. “Use of [risk-reducing salpingo-oophorectomy] and ovarian screening was reported in a sizable percentage of non-BRCA carriers despite insufficient data to determine the effectiveness of these interventions.”
The findings demonstrate that genetic testing, even if results are negative, “does not always allay deep-seated fears of cancer,” Victor Grann, MD, MPH, and Maxine Ashby-Thompson, MPH, both of Columbia University in New York, wrote in an accompanying commentary.
“Cancer biology is in the midst of a major transition that has led from a primary focus on oncogenes to a focus on systems,” Grann and Thompson wrote. “The challenge of the field is to identify persons needing additional or different treatment without scaring those who do not into additional interventions.”
Perspective
Back to TopPauline Funchain, MD and Charis Eng, MD, PhD, FACP
Cancer genetics has come of age. Many of the known hereditary cancer predisposition genes were discovered in the 1990s, and it has taken a good 2 decades to gather data regarding syndrome-specific management of disease in the context of inherited cancer predisposition genes. The article by Mannis and colleagues demonstrates the richness of information that has been and is currently being discovered regarding cancer predisposition syndromes and what kind of information is still under investigation.
Timely discovery of a cancer predisposition gene such as BRCA1 or BRCA2 can facilitate patient and practitioner decisions regarding surgical options such as risk-reducing bilateral salpingo-oophorectomy (RRSO), which essentially reduces the absolute lifetime risk of ovarian cancer in BRCA carriers from 40% to close to zero. Such interventions, when timely, can be life saving — especially with cancers, such as ovarian cancer, that have less-than-ideal screening modalities.
However, these interventions are not without adverse events, as every geneticist has the one story about a fatality from prophylactic, what-should-have-been-life-saving surgery. Mannis and colleagues demonstrate that genetic testing can effectively risk stratify, and thus personalize, medical decisions. In their study, almost 70% of BRCA mutation-positive individuals elected to undergo RRSO, as opposed to 2% of BRCA mutation-negative individuals. Testing thus saves unnecessary postoperative complications for mutation-negative individuals, as well as unnecessary medical expenditure, while heightening surveillance for mutation-positive individuals.
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