Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk

被引：35

作者：

Idos, Gregory E. ^{[1
]}

Kurian, Allison W. ^{[2
]}

Ricker, Charite ^{[1
]}

Sturgeon, Duveen ^{[1
]}

Culver, Julie O. ^{[1
]}

Kingham, Kerry E. ^{[2
]}

Koff, Rachel ^{[2
]}

Chun, Nicolette M. ^{[2
]}

Rowe-Teeter, Courtney ^{[2
]}

Lebensohn, Alexandra P. ^{[2
]}

Levonian, Peter ^{[2
]}

Lowstuter, Katrina ^{[1
]}

Partynski, Katlyn ^{[1
]}

Hong, Christine ^{[1
]}

Mills, Meredith A. ^{[2
]}

Petrovchich, Iva ^{[2
]}

Ma, Cindy S. ^{[2
]}

Hartman, Anne-Renee ^{[3
]}

Allen, Brian ^{[3
]}

Wenstrup, Richard J. ^{[3
]}

Lancaster, Johnathan M. ^{[3
]}

Brown, Krystal ^{[3
]}

Kidd, John ^{[3
]}

Evans, Brent ^{[3
]}

Mukherjee, Bhramar ^{[4
]}

McDonnell, Kevin J. ^{[1
]}

Ladabaum, Uri ^{[2
]}

Ford, James M. ^{[2
]}

Gruber, Stephen B. ^{[1
]}

机构：

[1] Univ Southern Calif, Los Angeles, CA 90089 USA

[2] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[3] Myriad Genet, Salt Lake City, UT USA

[4] Univ Michigan, Ann Arbor, MI 48109 USA

来源：

JCO PRECISION ONCOLOGY | 2019年 / 3卷

关键词：

OVARIAN-CANCER; MEDICAL GENETICS; AMERICAN-COLLEGE; SEQUENCING PANEL; BREAST; SUSCEPTIBILITY; MUTATIONS; IMPACT; GUIDELINE; VARIANTS;

D O I：

10.1200/PO.18.00217

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations. PATIENTS AND METHODS This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate). RESULTS Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested. CONCLUSION In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results. (C) 2018 by American Society of Clinical Oncology

引用

页码：1 / 12

页数：12

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