NCHR Comment on the USPSTF’s Draft Recommendations for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing

Thank you for the opportunity to express our views on the draft research plan for Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-related cancer risk.[1]

The National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts who analyze and review research on a range of health issues.

Based on its previous review, the USPSTF recommended risk assessment, genetic testing, and counseling for women with a family history of clinically important mutations in BRCA1 or BRCA2 genes.[2] However, as noted in the recommendations, there were a limited number of good quality studies that looked at long-term risks and consequences of testing for BRCA1/2 gene mutations. Additionally, only poor evidence was available to determine the risks and benefits for women without a family history.

We appreciate and support the USPSTF’s efforts to review and update recommendations based on evolving research. The current draft research plan has the potential to identify relevant research for the review and subsequent recommendations. We want to emphasize some points that we consider particularly pertinent.

The evidence regarding the likelihood of developing cancer for women with BRCA1 or BRCA2 mutations continues to evolve.  Shortly after mutations were discovered to increase risk for cancer, women were told that their cumulative risk of developing breast cancer or ovarian cancer was close to 100% for BRCA1 mutations and only slightly lower for BRCA2 mutations. Those estimates have decreased substantially since then, and according to the most recent estimates, around 55% to 65% of women who inherit BRCA1 mutations and around 45% of women who inherit BRCA2 mutations will develop breast cancer by age 70.[3] In addition, 39% of women who inherit the BRCA1 mutation and 11% to 17% of women who inherit the BRCA2 mutation will develop ovarian cancer by age 70. Despite these statistics, women who have lower chances of developing BRCA-related cancer due to the type of mutation and/or their age, still tend to believe that their lives are in immediate danger, with prophylactic surgery being the only real option. To make meaningful recommendations concerning screening, testing, and counseling around BRCA-related cancers, it is important to determine which BRCA1/2 mutations are clinically relevant, how they affect the likelihood of developing BRCA-related cancer and by what age they are likely to develop cancer, preferably 50, 60 and 70.

If a woman is diagnosed with clinically significant BRCA1/2 mutations, the major options are prophylactic medications, bilateral mastectomy or oophorectomy, or active surveillance.  All come with serious health risks, which means that the potential harm from screening, testing, counseling, and interventions can be serious.  The risks range from false security (and less vigilance) to unnecessary anxiety due to false positives resulting from inaccurate testing or poor counseling.

Poor or limited counseling, confounded by the lack of accurate, up-to-date information about the risks of treatment and management options, also may harm women who choose prophylactic treatments or surgery. Prophylactic surgery causes hormonal changes and self-image issues.  For women choosing mastectomy with reconstruction with breast implants, for example, there are known and unknown risks, including the possible development of ALCL, a type of lymphoma.  ALCL was thought to be extremely rare, but research now indicates that it is less rare than expected and can be caused by breast implants.[4]

The benefits and harms of testing, detection, and early intervention can differ for women of different age groups, socioeconomic status, ethnic origin and insurance status, in addition to family history of BRCA1/2 mutations. The research review and subsequent recommendations will be more beneficial if they are based on diverse populations, with subgroup analyses whenever possible to enable the USPSTF to determine if there are some demographic groups for which recommendations should be different.

In conclusion, we support The USPSTF’s efforts to provide updated recommendations on risk assessment, genetic counseling, and genetic testing on BRCA-related cancer, based on quality, up-to-date scientific studies. We hope the review will quantify the benefits and harms of each step starting with screening, in order to help USPSTF to make meaningful recommendations for appropriate subpopulations of women.

For questions or more information, please contact Stephanie Fox-Rawlings at

  1. USPSTF Draft Research Plan Draft Research Plan for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing, March 2017.
  2. USPSTF Final Recommendation Statement BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing, December 2013.
  3. “BRCA1 and BRCA2: Cancer Risk and Genetic Testing.” National Cancer Institute, National Institute of Health, April 2015.
  4. Safety Alerts for Human Medical Products- Breast Implants: Update- Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), March 2017.