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Multigene panels enjoy a broad psychological acceptance by patients
CA: A Cancer Journal for Clinicians  (IF508.702),  Pub Date : 2021-04-30, DOI: 10.3322/caac.21667
Mike Fillon

Key Points

  • Ninety‐two percent of the study participants “never,” “rarely,” or only “sometimes” reacted negatively to multigene panel results.
  • Carriers of high‐ and moderate‐risk pathogenic variants (PVs) had higher levels of uncertainty and distress regarding the panels, whereas patients with a variant of uncertain significance (VUS) or negative findings had lower levels of uncertainty and distress regarding the panels.

Dr. Idos says that one concern raised by critics of multigene panels is the high VUS rate and the potential for distress and uncertainty among these variant carriers. “However, our study showed that the psychologic response of VUS carriers matched the response of the patients testing negative.”

With the increased use of germline multigene panel testing for assessing inherited cancer risk, little is known about the acceptance of these tests—or the fear of them—by patients of ethnically diverse and economically disadvantaged groups who are known or possible carriers of mutations in cancer‐related genes. A new study conducted at multiple academic sites in California reported broad approval of the tests by patients. That study appears in Cancer (published online December 15, 2020. doi:10.1002/cncr.33357).

“We found that multigene panel testing is psychologically safe to use among a diverse population of patients undergoing genetic counseling,” says lead study author Julie O. Culver, MS, CGC, a clinical instructor of medical oncology at the University of Southern California (USC) Norris Comprehensive Cancer Center in Los Angeles.

Culver says that what prompted the study were concerns that the use of multigene panels would lead to confusion, uncertainty, and psychological distress in patients. “Our study … refutes some of the apprehension surrounding the use of multigene panels.”

According to study coauthor Gregory E. Idos, MD, MS, associate clinical professor at the Center for Precision Medicine at the City of Hope National Medical Center in Duarte, California, this study is also one of the first to measure the psychological response to genetic testing among moderate‐risk mutation carriers. “We found that the vast majority of moderate‐risk mutation carriers rarely feel uncertainty or distress about the tests,” he said.

Study coauthor Charité Ricker, MS, CGC, clinical instructor of medicine in medical oncology at USC, who practices at the Los Angeles County–USC Medical Center, added that most studies of psychological responses to testing have been conducted among college‐educated, mostly White or Ashkenazi Jewish individuals. “Our study included a mix of diverse backgrounds including non‐English speaking, Hispanic, and Asian individuals as well as many with a high school education or less.”

Study Details

The 1264 participants in the study were drawn from 3 genetics clinics: the USC Norris Comprehensive Cancer Center, the Los Angeles County–USC Medical Center, and the Stanford University Cancer Institute. All were patients of one of the clinics between July 2014 and November 2016. Participants were deemed eligible if statistical models indicated that either 1) they had at least a 2.5% probability of PVs in genes related to hereditary cancer or 2) they met National Comprehensive Cancer Network (NCCN) guideline criteria for genetic testing.

The participants received counseling by board‐certified genetic counselors or an advanced practice genetics nurse practitioner. Approximately a third of the subjects also met with a physician specializing in cancer genetics. Each participant was tested with a Myriad myRisk 25‐ or 28‐gene panel and completed a result survey, including the Multidimensional Impact of Cancer Risk Assessment (MICRA), at the baseline and after 3 months.

The study participants were predominantly female (79.8%) and had a mean age of 52.2 years; 70% of the participants had cancer. Non‐Hispanic Whites were the largest group at 44.9%. In addition, 37.3% identified as Hispanic, 9.7% identified as Asian, 3.2% identified as Black, and 4.9% identified themselves as “another race or ethnicity” or had mixed ancestry. Approximately 27.7% had an educational attainment of less than a high school diploma, and 22.7% were non–English‐speaking.

Study Results

The researchers found the following:
  • 7.4% of the subjects had a high‐risk PV.
  • 5.5% of the subjects had a moderate‐risk PV (moderate‐risk genes included those that presented a 2‐ to 5‐fold relative risk of cancer when altered by a PV).
  • 35.0% of the subjects had a VUS.
  • 52.1% of the subjects tested negative.

They also discovered that 92.4% of the participants had a total MICRA score of no greater than 38. This, they reported, meant that the vast majority of patients “never,” “rarely,” or only “sometimes” reacted negatively to the multigene panel findings. “Because the MICRA scale does not have recognizable thresholds for identifying psychologic distress,” says Culver. “We developed a green‐amber‐red scale that corresponds to MICRA responses to improve the interpretation of the original MICRA scale.”

As expected, the study reported that participants with a high‐ or moderate‐risk PV had much higher uncertainty, distress, and total MICRA scores coupled with significantly fewer positive experiences than did participants with a VUS or negative result. Specifically, using a multivariate analysis, the researchers reported that mean total MICRA scores were significantly higher, which meant greater uncertainty and distress, for high‐risk PV carriers (90 patients; mean MICRA score, 29.7) and moderate‐risk PV carriers (68 patients; mean MICRA, score 24.8) than they were for carriers of a VUS (424 patients; mean MICRA score, 17.4) or for patients who had negative results (623 patients; mean MICRA score, 16.1). These results agree with previous studies, with high‐risk PV carriers having higher total MICRA scores.

The researchers also found that having a cancer diagnosis or less formal education was associated with a significantly higher total MICRA score, whereas race and/or ethnicity was not related to total MICRA scores.

Dr. Idos says that one concern raised by critics of multigene panels is the high VUS rate and the potential confusion among these gene carriers. “However, our study showed that the psychologic response of VUS carriers matched the response of the patients testing negative.” He added, “Because the MICRA scale does not have recognizable thresholds for identifying psychologic distress, we developed a green‐amber‐red scale that corresponds to MICRA responses to improve the interpretation of the original MICRA scale.”

Study Analysis

“This study breaks new ground,” says Tuya Pal, MD, associate director for cancer health disparities and the Ingram Professor of Cancer Research at the Vanderbilt‐Ingram Cancer Canter in Nashville. “While we have a lot of data on the BRCA1 and BRCA2 and what we consider the regular high‐penetrance genes, we don't know as much about the psychosocial outcomes of individuals who have moderate penetrance risk genes.”

Dr. Pal says a key strength of the study was the diversity of its participants, who received counseling by professionals, which she says no doubt helped with the high acceptance rates. “Often, when we think about genetic testing studies, particularly for ones that are clinic‐based, we're not seeing diversity in the patient population,” she says. “Here, they had pretty good representation of Hispanics and Asians, which is not common in US‐based studies.” Dr. Pal did note that there was a fairly low number of African American patients, which is a study limitation. “Additionally, while these results are encouraging for those who receive genetic counseling through a genetics professional prior to testing, it should be recognized that that vast majority (~80%) of patients are tested out in the community without interfacing with someone with expertise in genetics. Consequently, it is critical to evaluate outcomes when patients are tested out in the community without the involvement of a genetics professional.”

“The reason we do genetic testing is so that we can positively influence care,” says Dr. Pal. “While we know that genetics is only one piece of healthy outcomes, if we roll genetic testing out more broadly but we don't address disparities across diverse populations and the ability to pay, we're just going to widen the divide between those who have access to great care and those who don't … we're going to increase those disparities.”

Culver agrees. “Further research would help clarify whether the same results would be found among patients who receive genetic testing from other types of health care providers and in community settings.”

Dr. Pal is also the vice‐chair of the panel for the NCCN Guidelines for Genetic/Familial High‐Risk Assessment: Breast, Ovarian and Pancreatic Panel and encourages clinicians looking for guidance on this topic to use these guidelines as a resource. Anyone can access these guidelines by creating a free account through the NCCN website (

Another recommended resource, hosted by the National Cancer Institute and for which Dr. Pal will be the incoming editor‐in‐chief, is PDQ Cancer Information Summaries: Genetics (‐summaries/genetics). “This is a resource that is updated on a monthly basis as new information relevant to the field of inherited cancer predisposition is published,” says Dr. Pal.