Longitudinal outcomes with cancer multigene panel testing in previously tested BRCA1/2 negative patients

Abstract

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months. Of 317 eligible BRCA1/2 negative patients who discussed the study with research staff, 249 (79%) enrolled. Decliners were more likely to be older, non-White, and recruited by mail or email. Ninety-five percent of enrolled patients proceeded with MGPT. There were no significant changes in anxiety, depression, cancer specific distress or uncertainty postdisclosure. There were significant but small increases in knowledge, cancer-specific distress and depression at 6-12 months. Uncertainty declined over time. Those with a VUS had significant decreases in uncertainty but also small increases in cancer specific distress at 6 and 12 months. Among those with a positive result, medical management recommendations changed in 26% of cases and 2.6% of all tested. Most BRCA1/2 negative patients have favorable psychosocial outcomes after receipt of MGPT results, although small increases in depression and cancer-specific worry may exist and may vary by result. Medical management changed in few patients.

Keywords: cancer genetic testing; cancer prevention and screening; delivery of genetic services; genetic testing outcomes; multigene panel testing.

Figure 1:. Study Consort

^a Includes individuals who provided permission to be contacted during a clinic visit but never responded to recruitment attempts ^b Ineligibility due to: offered a competing study (7), already had panel testing (6), previously tested positive for a genetic mutation (3), did not have prior BRCA1/2 testing (2), deceased (1), clinician request (1) ^c three participants proceeded with a targeted custom panels. ^d APC (9), ATM (4), BRCA1 (2), BARD1, CDH1, CHEK2 , APC/CHEK2, MUTYH (het), NBN, PALB2, TP53 ^e ATM (18), APC (7), CHEK2 (6), APC/CHEK2 (3), BRIP1 (3), RAD51D (3), SMAD4 (3), ATM/NBN (2), BMPR1A (2), BRCA1 (2), CHD1 (2), MSH6 (2), NBN (2), PMS2 (2), RAD51C (2), APC/CDH1, ATM/PMS2, ATM/BMPR1A, ATM/TP53, BARD1, BARD1/MSH2, BRCA1/MUTYH, BRCA2, BRIP1/CDKN2A, BRIP1/CHEK2, CDK4/CHEK2, CDKN2A, CDKN2A/TP53, CHEK2/STK11, MLH1, MUTYH/RAD51D, STK11.

Figure 2:. Longitudinal Change in Patient Reported Cognitive and Affective Outcomes in ALL PARTICIPANTS and BY RESULT

Everyone = All Participants Negative = Uninformative Negative Result Positive = Positive Result VUS = Variant of Uncertain Significance Result Baseline=0–7 Days after consent, Pre-Disclosure=0–7 Days after pre-test counseling, Post-Disclosure=0–7 Days after result disclosure counseling, 6 Mo=6 Months after disclosure counseling, 12 Mo=12 Months after disclosure counseling. Did not examine Baseline to Pre-Disclosure changes since the participants did not know results at the time of Pre-Disclosure. All findings not statistically significant unless indicated.

Figure 2:. Longitudinal Change in Patient Reported Cognitive and Affective Outcomes in ALL PARTICIPANTS and BY RESULT

Everyone = All Participants Negative = Uninformative Negative Result Positive = Positive Result VUS = Variant of Uncertain Significance Result Baseline=0–7 Days after consent, Pre-Disclosure=0–7 Days after pre-test counseling, Post-Disclosure=0–7 Days after result disclosure counseling, 6 Mo=6 Months after disclosure counseling, 12 Mo=12 Months after disclosure counseling. Did not examine Baseline to Pre-Disclosure changes since the participants did not know results at the time of Pre-Disclosure. All findings not statistically significant unless indicated.