CHICAGO — Multiplex gene testing of diverse patients has found that patients who test positive advise relatives to test, “suggesting that participants understood the implications of test results,” according to results of a planned interim analysis of a prospective trial presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.1

The study also found that based on test results, few patients reported preventive surgery at the 3-month follow-up and those with genetic variant of uncertain significance had no more distress, regret, or uncertainty than those who tested negative, said Allison W. Kurian, MD, MSc, Stanford University Cancer Institute, Stanford, California.

“Sequencing more genes increases the chance of finding a pathogenic mutation and/or a variant of uncertain significance,” she said; however, “little is known about potential harms of multiplex testing for cancer risk, such as unwarranted surgery or adverse psychological effects.”

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The prospective cohort study of the multiplex gene panel opened in August 2014 in cancer genetics clinics at LA County, USC, and Stanford University. The 25-gene panel sequenced APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53.

Eligible patients were those who met standard testing guidelines or predictive models that estimated 2.5% or greater mutation probability. The validated Multidimensional Impact of Cancer Risk Assessment (MICRA) scale, which measures distress, uncertainty, and positive experiences, was used to survey patients 3 months after their genetic test, results of which Dr. Kurian reported; surveys will also be conducted at 6 months and then annually thereafter.

Of 1000 of the planned 2000 total participants, 11.6% tested positive for a pathogenic mutation, 36.5% had variant of uncertain significance only, and 51.9% tested negative. Median age was 51 years; 82% were female; 40.4% were Hispanic; and 74.3% had a personal history of cancer, primarily breast cancer (37.6%); 25.7% reported no cancer.

At 3 months, self-reported preventive surgery rates were low: bilateral mastectomy, 3.2%; unilateral mastectomy, 5.8%, hysterectomy, 1.5%; and bilateral and unilateral oophorectomy, 0.8% for both.

“Most patients never or rarely had thoughts of cancer affecting daily activities,” said Dr. Kurian; these rates were 58.7% among those who tested positive; 70.8% for variant of uncertain significance; and 69.6% for those who tested negative.

Scores of mutation-positive patients differed significantly from those of negative patients and of those with variants of uncertain significance for all MICRA components (P < .0010), Dr. Kurian said. Scores of patients with variants of uncertain significance did not differ significantly from those of negative patients for any MICRA components.



1. Kurian AW, Idos G, Culver J, et al. Safety of multiplex gene testing for inherited cancer risk: Interim analysis of a clinical trial. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.