This is the first U.S. report to prospectively examine the full spectrum of long term risk management outcomes and predictors following BRCA1/2
testing. At a mean of 5.3-years post testing, this report provides the longest follow-up to date. After testing, 37% of BRCA1/2
carriers opted for RRM and 65% of opted for RRBSO. Overall, 91.2% of affected carriers and 63.9% of unaffected carriers obtained RRM and/or RRBSO prior to or following testing (data not shown). The 40.3% RRM uptake among affected carriers and 32.6% among unaffected carriers are comparable to17,18
or higher than15,16
previous U.S. reports. Our sample also had comparable or slightly higher uptake of RRBSO compared to prior reports.15,16,18,24,25
These rates likely reflect our longer follow-up time compared to previous studies.15–18
Our rates may also reflect a trend of increasing use of these surgeries. Recent reports indicate rising use of contralateral RRM among newly diagnosed breast cancer patients.38–41
These data, coupled with emerging evidence of reduced mortality following risk reducing surgery,7
suggest that BRCA1/2
testing may beneficially impact cancer mortality.
Unique to this report was our evaluation of prospective predictors of RRM and RRBSO. Our finding that age was the only predictor of RRBSO among carriers reflects current guidelines recommending RRBSO by age 40.23,42
RRM was associated with having intact ovaries and higher anxiety at the time of genetic counseling. Given the risk reduction associated with oophorectomy, individuals who had a prior oophorectomy may have been less motivated to consider RRM. The association between anxiety and RRM contrasts with the only prior report to examine psychosocial predictors of long-term RRM.20
However, it is consistent with prior studies documenting an association between distress and RRM in the year following testing.13,31,32
These data highlight the paradox that while distress tends to be low among carriers,33
even low level distress may impact management decisions.
Although limited by a small sample, we found that 17% of unaffected carriers reported using tamoxifen or raloxifene. These data contrast with recent reports indicating low overall use in the U.S.43,44
However, these estimates are consistent with a prior study in which 12.4% of unaffected U.S. carriers reported using tamoxifen.18
These data suggest that chemoprevention may be a viable management alternative for some BRCA1/2
test results are the most common result encountered in clinical practice and are associated with heterogeneous and difficult to quantify breast and ovarian cancer risks. Consistent with the limited prior research,45,46
we found low rates of contralateral RRM (7%) and RRBSO (13.3%) among uninformatives. The greater uptake of contralateral RRM among younger patients likely reflects their higher lifetime risk compared to older patients. Predictors of RRBSO were perceived risk for breast cancer and having an RRM prior to genetic counseling. The fact that women with prior RRM were more likely to opt for RRBSO was not expected as uninformative test results are not typically associated with increased ovarian cancer risk. It is likely that both RRM and RRBSO reflect an overall greater perception of vulnerability to cancer. This is consistent with the fact that perceived risk for breast cancer was also associated with receipt of RRBSO.
Although mammography use was uniformly high, use of MRI was strongly associated with test result. Almost half of mutation carriers reported that they had received a screening MRI. Prior research has reported rates of MRI among U.S. and Canadian carriers ranging from about 25% to 48%.18
Our results might reflect increased MRI screening consistent with the addition of annual MRI to management guidelines.29
We also examined ovarian cancer screening. Consistent with prior studies and with the lack of demonstrated efficacy, rates of CA-125 and TVU were lower than rates of breast cancer screening. However, carriers were more likely than uninformatives and negatives to receive ovarian cancer screening.
The generalizability of these data are limited by the fact that they were collected from a single institution in which all participants were enrolled in clinical research studies. However, it is important to note that referrals were drawn from a diverse group of community providers across a large metropolitan area. The sample likely reflects the population typically seen at large cancer genetics referral centers. Even so, the fact that only 6% of participants were members of racial/ethnic minorities and 95% were college educated indicates that these results must be interpreted cautiously.
Despite these limitations, this is the first U.S. study to prospectively evaluate the full spectrum of long-term management outcomes and predictors. With an average follow-up time of 5.3 years, this study provides a clearer picture of long-term decision making following testing. Our data document that the majority of carriers engage in RRM and/or RRBSO. These data, combined with reports of the risk and mortality reduction benefits of these behaviors, strongly suggest that the receipt of a positive BRCA1/2 test result is likely to have a favorable impact on long-term breast and ovarian cancer outcomes.