The U.S. Preventive Services Task Force (USPSTF) has published new recommendations regarding risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility 1 and 2 genes (BRCA1/2)-related cancer. According to the updated guidelines, more women should be assessed for BRCA1/2 gene mutations.
According to a summary of the recommendations, published in JAMA, “The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with breast cancer susceptibility 1 and 2 (BRCA1/2) gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing.” The recommendation is B-grade, meaning it is recommended with “high certainty” that the benefit is moderate to substantial.
Current USPSTF recommendations state that a family risk assessment tool should be used to determine which women should undergo #genetictesting for BRCA1/2 mutations. Fox Chase clinical #genetics specialist Dr. Kristen Whitaker shares her perspective: https://t.co/1TN6ldomLy.
— Fox Chase Cancer Center (@FoxChaseCancer) August 20, 2019
“In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases,” according to the summary.
The previous recommendation, updated most recently in 2013, did not include this population of women—only women with a family history of the aforementioned cancers were included. This guideline suggests that women with a personal history of one of those cancers, even if they have been deemed cancer-free, should also be evaluated, as well as women with ancestry considered high-risk for either the BRCA1 or BRCA2 mutations.
Take a look at US Preventive Services Task Force (USPSTF) updated recommendations for risk assessment, genetic counseling, and genetic testing for BRCA-Related Cancer in #JAMA!! #OncoAlert https://t.co/j4EPt3RJ7x
— pvukovic (@VukovicPetra) August 20, 2019
Women who do not have a family history associated with either of the mutations should not receive routine genetic counseling or testing, per the USPSTF’s recommendation. This recommendation is D-grade, meaning the service is not recommended and that there is “high certainty” that the risks would not outweigh the benefits.
To make this updated recommendation, the USPSTF queried MEDLINE, PsycINFO, and EMBASE, for updates (Jan. 1, 2013, to March 6, 2019) and new key questions and populations (Jan. 1, 1994, to March 6, 2019), as well as reference lists. Eligible studies were discriminatory accuracy and observational studies as well as randomized clinical trials (RCTs) analyzing women without recently diagnosed BRCA1/2-related cancer. The primary outcomes were cancer incidence and mortality and discriminatory accuracy of risk assessment tools, as well as the benefits and harms associated with risk assessment, genetic counseling and testing, and risk-reducing interventions.
The final analysis included 110 articles written about 103 studies encompassing 92,712 patients. None of the included data were about how effective risk assessment, genetic counseling, and genetic testing were in reducing BRCA1/2-related cancer incidence and death. A total of 14 studies including 43,813 patients found that eight risk assessment tools presented “moderate to high accuracy” in guiding referrals to genetic counseling, with an area under the receiving operating characteristic curve of 0.68–0.96. A total of 28 studies with 8,060 patients found an association between genetic counseling and reductions in breast cancer worry, anxiety, depression, and testing intention, and an increase in risk understanding. In 22 studies (n = 4,322), women who tested positive had higher breast cancer worry and anxiety compared to other patients, while testing was also associated with a higher risk understanding.
“In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers,” the researchers wrote in their updated evidence report, also published in JAMA.
Six studies (n = 2,546) found a 90% to 100% reduction in breast cancer incidence associated with mastectomy, and one study (n = 639) found an 81% to 100% reduction in mortality. According to two studies with 2,108 patients, “oophorectomy was associated with 69% to 100% reduction in ovarian cancer.” Mastectomy often led to complications.
— Michael Walter (@MichaelWalterRB) August 20, 2019
The evidence report concluded, “Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.”