USPSTF: Screen women with increased risk for BRCA1, BRCA2 mutations

The USPSTF recommends that primary care clinicians should assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have known family members with BRCA1/BRCA2 mutations using validated risk screening tools. The recommendations further clarify that, if screening for hereditary breast cancer, genetic counseling and, if indicated, genetic testing for BRCA is done, the benefits outweigh the harms and has an impact on risk screening for patients (and potentially their family members).

Consideration of screening for potentially harmful BRCA mutations should begin once women have reached the age of consent (18 years). Primary care providers should periodically assess all patients for changes in family history (for example, comprehensive review at least every 5 to 10 years). Although several risk tools are available, the tools evaluated by the USPSTF include the Ontario Family History Assessment Tool, Manchester Scoring System, Referral Screening Tool, Pedigree Assessment Tool, and FHS-7.

Mutations in BRCA1 and BRCA2 increase the risk of several cancers in addition to breast and ovarian cancer. Other BRCA-related cancers include pancreatic cancer, prostate cancer and melanoma. These cancers should be also considered when evaluating an individual for BRCA testing.

Finally, there are other hereditary genes related to breast cancer, such as CHEK2, PALB2, ATM and others. Unfortunately, there are no clear screening and guidelines for the evaluation of these genes and therefore often these genes are included in the panel when BRCA is ordered.

The 2019 update to the USPSTF recommendation on risk assessment, genetic counseling and genetic testing for BRCA-related cancer highlights that there is moderate benefit of risk assessment, genetic counseling and testing, and interventions only for women whose family or personal history or ancestry is associated with increased risk of BRCA1/2 mutations. It also recommends that primary care clinicians use one of several familial risk assessment tools to determine who should be referred for genetic counseling and possible genetic testing.

While these recommendations generally align with current clinical practice, several points are worth noting. Using family history to guide who should receive genetic testing opens the door for missed opportunities to identify a mutation. Recent studies have demonstrated that rates of mutations identified in individuals meeting family history criteria for testing and those not meeting such criteria were similar. Furthermore, one study demonstrated that when restrictive family history criteria is a necessary criteria for determining who should be tested, nearly 50% of individuals with pathogenic/likely pathogenic mutations could be missed.

However, until we have more studies confirming such findings and have determined an alternate way to appropriately identify individuals with the highest risk of carrying a BRCA1/2 mutation, using family history along with personal history to guide genetic testing remains appropriate. The lack of recommendation for the use of multigene panels will need to continue to be evaluated as studies have demonstrated the use of multigene panels results in identifying more clinically actionable mutations. In the case of breast cancer predisposition genes, there identification is important as the presence of such mutations could change the clinical management of the woman. Further research into the current practices regarding utilization of multigene panels and clinical outcomes of women who have non-BRCA1/2 genes identified will be important to determine whether this recommendation should be changed in the future. It will also be important that clinicians undergo training and become comfortable managing variants of uncertain significance that increase when multigene panel tests are performed — this should happen before multigene panels become widely recommended by guidelines.

Lastly, although primary care clinicians are the ideal group to assess risk and make appropriate referrals for genetic counseling, it will be important to assess the feasibility of using the recommended familial risk assessment tools among busy primary care clinicians who already have many other demands and time restraints while in clinic.

Of these new USPSTF recommendations, primary care physicians should especially note the addition of breast, ovarian, tubal, or peritoneal cancer as indicators to identify women who may carry mutations in the BRCA1 and BRCA2 genes. Patients who had one of those cancers years ago may not appreciate that they should consider genetic testing. As good clinicians, it’s our responsibility to keep our patients as healthy as possible. Identifying patients with mutations in BRCA1/BRCA2 can help to identify those at risk for additional cancers. 

The task force weighs the information in the studies they review before they assign a recommendation a grade. There are some in medical community, including those who study genomics, that think the “D” recommendation in these new USPSTF recommendations misses an opportunity to prevent cancer-related deaths. These critics cite factors such as cost of genetic testing dropping in recent years and that these tests cover many more conditions than they once did. In the United States, Geisinger is doing large-scale testing that could detect even more at-risk patients. These points, taken together, suggest to some that the benefits of genetic testing may outweigh the risks, in some women who don’t have a prior personal or family history of breast, ovarian, tubal, and/or peritoneal cancer, such as individuals of Ashkenazi Jewish ancestry. Perhaps with more time, the USPSTF will have more evidence to assess and will change the “D” to a higher grade. Time will tell.