Screening and Risk-reduction without Testing Positive for BRCA Mutation

Get Permission

Many women who do not test positive for a BRCA mutation undergo additional ovarian cancer screenings and risk-reducing procedures, despite limited data to determine the effectiveness of these interventions among an average-risk population. Results of an analysis of data from 1,077 women who were surveyed at a median of 3.7 years after BRCA screening, were published online first by the Archives of Internal Medicine. The women were asked about their subsequent risk-reducing and screening interventions, including risk-reducing salpingo-oophorectomy, screening transvaginal ultrasonography, and screening serum cancer antigen 125 (CA-125).

BRCA test results were categorized as positive (shown to carry known deleterious BRCA mutation) in 201 (18.7%) of these women, true-negative (negative test result for a known deleterious family BRCA mutation) in 103 women (9.6%), and uninformative negative (negative BRCA results without a known family mutation) or variant of undetermined significance (found to have a change in DNA that has unknown effects on BRCA protein function) in 773 women (71.8%).

Women who tested positive as BRCA mutation carriers “were the most likely to receive aggressive interventions, with a 69.8% use of [risk-reducing salpingo-oophorectomy] and a 28-fold higher odds of receiving [that procedure] compared with women with uninformative BRCA results,” the researchers reported. But many who were not identified as BRCA carriers also received aggressive interventions.

“More than 70% of BRCA-tested women in this study—and in the United States—receive uninformative results. In this understudied but important population, a substantial proportion underwent [salpingo-oophorectomy] (12.3%) and reported receiving ovarian cancer screening (30.2%) at least once in the preceding 3 years. Long-term ovarian cancer risk in women with uninformative BRCA results has not been carefully defined,” the researchers noted. “For most women with uninformative BRCA results, salpingo-oophorectomy and ovarian cancer screening may not be appropriate, barring strong family histories of ovarian cancer.”

Key Findings

Overall, 19.1% of eligible women underwent risk-reducing salpingo-oophorectomy and 39.6% percent used screening procedures. Women who received a positive BRCA test result had increased odds of undergoing salpingo-oophorectomy, transvaginal ultrasound, and serum CA-125, while a true-negative BRCA result was associated with reduced odds of undergoing the three procedures. When the researchers compared screening rates in the preceding 3 years on the basis of BRCA results, they found that approximately 69.6% of BRCA carriers, 30.2% percent of women with uninformative BRCA results, and 9.6% percent of women with true-negative BRCA results reported having undergone ovarian cancer screening.

The study “shows that genetic testing, even if negative, does not always allay deep-seated fears of cancer,” noted an accompanying commentary. “The challenge of the field is to identify persons needing additional or different treatment without scaring those who do not into additional interventions.”

Mannis GN, et al: Arch Intern Med, December 17, 2012 (early release online).

Grann V, Ashley-Thompson, M: Arch Intern Med. December 17, 2012 (early release online).