Assessing the Genetic Risk for BRCA-Related Breast or Ovarian Cancer in Women: Recommendations From the U.S. Preventive Services Task Force Free

Rebecca Mueller, Susan M. Domchek, Katherin L. Nathanson

University of Pennsylvania

January 9, 2014

Concerns regarding the USPSTF on BRCA testing

The recently released USPSTF statement on Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women included important revisions from the draft statement released in April 2013, however it has several limitations. In particular, the exclusion of affected individuals (i.e. those with a personal history of cancer) is problematic. Although the statement notes that affected individuals may be the ideal candidate to undergo BRCA testing via screening of their unaffected relatives, it fails to recognize the preventive benefits associated with identification of genetic risk due to BRCA1/2 in individuals with a history of cancer. Women with a history of breast cancer not only “should be encouraged to discuss further evaluation with their clinician,” but should also have access to the screening and prevention for the second primary cancers that they are at significantly increased risk of developing. Primary providers may be helpful in identification of testing candidates who are no longer followed by oncology professionals. Secondary prevention strategies (particularly risk-reducing oophorectomy) significantly reduce cancer risk and mortality in this population.1 Additionally, this information allows family members to undergo single-site testing for the known mutation, or to avoid genetic testing if no mutation is identified in the affected individual, which is a more cost-effective and rational approach to testing within a family.

In addition, the statement fails to recognize:
1. That men may derive benefit from genetic testing for mutations in BRCA1/2. Male carriers have higher risks for male breast cancer, prostate cancer, melanoma, and pancreatic cancer. We believe it is inappropriate to exclude men as potential beneficiaries from mutation testing.
2. The challenges of testing women between ages 18-24. In general, specialized screening and prevention options are not initiated in female carriers until age 25.2 Knowing one is at high risk but not yet at the age to be screened should be part of the genetic counseling discussion for when to initiate testing.
3. That more comprehensive BRCA testing, beyond founder mutations, is sometimes indicated in individuals of Jewish ancestry.

Finally, we feel that the statement “Evidence is lacking on the effect of intensive screening for BRCA-related cancer on clinical outcomes in women who are BRCA mutation carriers” may be misleading to primary providers. Although there are no randomized studies, there are data to suggest an improvement in stage of diagnosis with intensive breast cancer screening.3

Sincerely,

Rebecca Mueller, MS, CGC
Genetic Counselor, University of Pennsylvania MacDonald Cancer Risk Evaluation Program
Philadelphia, Pennsylvania
Rebecca.mueller@uphs.upenn.edu

Susan Domchek, MD
Director, Basser Research Center for BRCA, University of Pennsylvania
Director, MacDonald Cancer Risk Evaluation Program
Abramson Cancer Center
Philadelphia, Pennsylvania
Susan.domchek@uphs.upenn.edu

Katherine L. Nathanson, MD
Associate Professor of Medicine, University of Pennsylvania
Co-Leader, Cancer Control Program
Chief Oncogenomics Physician
Abramson Cancer Center
Philadelphia, Pennsylvania
Katherine.nathanson@uphs.upenn.edu

On behalf of the University of Pennsylvania MacDonald Cancer Risk Evaluation Program


References:
1 Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010 Sep 1;304(9):967-75.
2 National Comprehensive Cancer Network [Internet]. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian- Version 4.2013 Hereditary Breast and/or Ovarian Cancer Syndrome, HBOC-A. Accessed online 1-6-2014. http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf
3 Passaperuma K, Warner E, Causer PA, Hill KA, Messner S, Wong JW, et al. Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer. 2012 Jun 26;107(1):24-30.