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PURPOSE: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer. METHODS: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing. We examined whether genetic test results were associated with CPM using multivariable logistic regression models. RESULTS: Among 707 racially or ethnically diverse women, most had benign or likely benign (B or LB) variants, whereas 12.5% had P or LP and 17.9% had VUS. Racial or ethnic minorities were twice as likely to receive VUS. Patients with P or LP variants had higher CPM rates than VUS or B or LB (64.8% v 25.8% v 25.9%), and highest among women with P or LP variants in high-penetrance genes (74.6%). On multivariable analysis, P or LP compared with B or LB variants were significantly associated with CPM (odds ratio = 4.24; 95% CI, 2.48 to 7.26). CONCLUSION: Women with P or LP variants on genetic testing were over four times more likely to undergo CPM than B or LB. Those with VUS had similar CPM rates as B or LB. Our findings suggest appropriate genetic counseling and communication of cancer risk to multiethnic breast cancer survivors.

Recent advances in next generation sequencing have enabled panel gene testing, or simultaneous testing for mutations in multiple genes for a clinical condition. With more extensive and widespread genetic testing, there will be increased detection of genes with moderate penetrance without established clinical guidelines and of variants of uncertain significance (VUS), or genetic variants unknown to either be disease-causing or benign. This study surveyed 232 patients who underwent genetic counseling for hereditary breast and ovarian cancer to examine the impact of panel gene testing on psychological outcomes, patient understanding, and utilization of genetic information. The survey used standardized instruments including the Impact of Event Scale (IES), Multidimensional Impact of Cancer Risk Assessment (MICRA), Satisfaction with Decision Instrument (SWD), Ambiguity Tolerance Scale (AT-20), genetics knowledge, and utilization of genetic test results. Study results suggested that unaffected individuals with a family history of breast or ovarian cancer who received positive results were most significantly impacted by intrusive thoughts, avoidance, and distress. However, scores were also modestly elevated among unaffected patients with a family history of breast and ovarian cancer who received VUS, highlighting the impact of ambiguous results that are frequent among patients undergoing genetic testing with large panels of genes. Potential risk factors for increased genetic testing-specific distress in this study included younger age, black or African American race, Hispanic origin, lower education level, and lower genetic knowledge and highlight the need for developing strategies to provide effective counseling and education to these communities, particularly when genetic testing utilizes gene panels that more commonly return VUS. More detailed pre-test education and counseling may help patients appreciate the probability of various types of test results and how results would be used clinically, and allow them to make more informed decisions about the type of genetic testing to select.