Increased Reach of Genetic Cancer Risk Assessment as a Tool for Precision Management of Hereditary Breast Cancer
Authors: Kathleen R. Blazer, Thomas Slavin, Jeffrey N. Weitzel
Journal: JAMA Oncology (2016)

Genetic cancer risk assessment (GCRA) is an interdisciplinary clinical practice that incorporates genetics, oncology, and counseling skills to quantify risk and implementmore precise care for individualswith inheritedcancerpredisposition.1GCRA is warranted for individuals with features suggesting hereditary cancer, such as early age at onset, triple-negative breast cancer, and/or a family history of breast or ovarian cancer. The cloning of theBRCA1 gene on chromosome 17 in 1994, and of a second high-risk locus (BRCA2) on chromosome 13 in 1995, ushered in an erawith increasing appreciation of the potential for oncogenetics to influence breast cancer screening, treatment, andprevention.Thesubsequentdecadeshavebeen marked by an ever greater understanding of gene-specific pathology and age-specific risk for BRCA-associated breast cancers, as well as a growing understanding of hormonal and genetic modifiers of risk.1 Commercial testing for BRCA1 and BRCA2 became available in theUnitedStates in1996,andprofessional societypolicy statements and practice guidelines affirm the value of BRCA testing for identifyingandmanaginghigh-risk individuals and families.2,3 In this issue, Rosenberg and colleagues4 describe BRCA gene testing and surgical decision-making outcomes amongparticipants in theYoungWomen’sBreastCancerStudy (YWS), amulticentercohortofwomen40yearsoryoungerwho had limited-stage breast cancer (ie, stage 0-II) and received GCRA at academic and community clinics between 2006 and 2014.Participantsweremostlywhite,well educated (85%completed college and/or graduate school), and virtually all had health insurance. One positive finding of the study was a relatively robust reach, in that most of the YWS study participants (87%) received BRCA gene testing within 1 year of their breast cancer diagnosis. While concerns have been expressed about proposed population-based BRCA testing for unaffected young women,5 we are heartened by the increasing participation in standard-of-care GCRA by young women with breast cancer. We concur with the authors4 that, unfortunately, it is unlikely that this level of access to, or participation in, GCRA would be found in the community setting or among the economically underserved or ethnic minorities. It is disconcerting that 48% of thosewho did not get testing indicated that they and/or their physician did not think a BRCA mutation was likely, despite the fact that the National Comprehensive Cancer Network (NCCN) guideline2 has recommended genetic counseling and BRCA testing for women with breast cancer diagnosed at 40 years or younger since the outset of the YWS study. The study results did not identify addeddistressasa reasonfordecliningBRCA testingat the time of cancer diagnosis, but the authors2 suggest this as a potential factor, referencingprevious studies that examinedand reported on this finding. The authors2 note the need to explain the practical purpose for genetic testing at the time of a new breast cancer diagnosis and address patient concerns. These issues are most consistently addressed as an essential component of pretest counseling when conducted by clinicians with expertise in GCRA. Comprehensive GCRA also addresses the challengesof conveying complex,uncertainoruninformative test results in a way that reduces confusion and uncertainty about risk management decision-making. Only a few participants (15) indicated concerns about genetic discrimination as a reason they declined BRCA testing. While historically a barrier to genetic testing, additional protectionswith theGenetic Information andNondiscriminationActof2008and lackofevidenceofgeneticdiscrimination6 have reduced these concerns in recent years. There is also a broadening social awareness andacceptability of genetic testing for hereditary predisposition. Thiswasmost dramatically evidencedduring the latterportionof theYWSsampling frame, when in May 2013 actress and director Angelina Jolie announced that she carries a BRCA1 mutation and chose to undergo a bilateral risk reductionmastectomy (RRM) and reconstruction. This announcement generated considerable interest in testing, evidenced by a surge in uptake of GCRA services and testing noted in the YWS study and others in the United States and internationally.7,8 It is notable that most of themedia sound bites on Jolie’s announcement included her clear admonition that although bilateralmastectomywas the answer forher, it is not always the answer—aqualification that is consistent with the NCCN guideline classification of RRM as an option for BRCA carriers.2 The YWS study2 reported a high uptake of RRM (86%) among the women diagnosed as having a BRCA mutation. While the precise timing of genetic testing relative to treatment decision-making was not reported in the study, the authors2 suggest that because testing took place within 3 months of diagnosis formost, andwithin 1 year for all participants, it is likely thatBRCA statuswas available at the time of surgical decision-making in context of breast cancer treatment. This finding is consistent with those of previous studies9-11documentingahighrateofRRMamongwomenwith newlydiagnosedbreast cancer identified asBRCA carriers, including an international study12 that noted significant variaRelated article page 730 Opinion