Genetic Testing Can Guide Treatment, but Access and Counseling Are Essential, Studies Say


Getting the full picture of genetic testing results requires that patients have access to genetic counselors who can evaluate individual risk.

Advances in genetic testing increasingly connect cancer patients with treatments that work—and help them avoid those that won’t. But providers have a responsibility to make sure they are ordering the right tests and using the results correctly, said Erin Hofstatter, MD, associate professor adjunct and co-director, Cancer Genetics and Prevention Program at Yale School of Medicine.

Getting the full picture means patients should have access to genetic counselors who can evaluate individual risk, Hofstatter said during Saturday’s virtual session, “Cancer Risk, Genetics, and Prevention,” part of the American Society of Clinical Oncology 2020 annual meeting.

Hofstatter highlighted 4 studies that she said amplify the 3 components of using genetic testing in cancer treatment and prevention: (1) understanding the germline component of a tumor test, (2) broadening access to genetic counselors with video sessions, and (3) making sure risk assessment of each patient is accurate, so that patients do not have surgeries they do not need.

MSK-IMPACT. Tumor tests typically look for acquired mutations—somatic testing—to select targeted therapies. This study evaluated the value, or clinical utility, of adding germline profiling, for inherited mutations, for patients with advanced cancer, through next-generation sequencing (NGS).1 From a study population of 11,975 patients, researchers identified 2043 (17.1%) who had pathogenic or likely pathogenic germline variants, including 777 patients (6.5%) who had genes for which targeted therapies were available. Most of these were for BRCA mutations (416) or for Lynch syndrome (149). Of importance, she said, is the share of patients with advanced disease who received a targeted therapy: the authors report 45.3% out of 554 patients.

But Hofstatter noted that such findings are essentially a moving target. “If emerging genes of interest in homologous recombination repair are included, prevalence rose to 8.6%,” she said.

“With the emergence of novel targeted treatments, it's important to realize that the therapeutic actionability of germline variants is likely to increase significantly over time,” and, increasingly, the advanced setting is where germline testing will be indicated to select a cancer treatment.

“It's important to know your test. Remember that tumor sequencing is not a substitute for control. Hence of germline testing, and it should be considered separately to achieve the best results,” Hofstatter said.

Improving access. Despite broader availability of germline testing, uptake is poor—only about 2% of Lynch syndrome carrier have been identified, Hofstatter said. Lack of knowledge, cost, inconvenience, and a shortage of genetic counselors—some payers require a session before testing—have all been barriers.

Two studies presented during ASCO examined whether there was any disadvantage for patients if counselors met with them via telemedicine—a method that has taken off in recent months due to the COVID-19 pandemic. The ProGen study, led by Huma Q. Rana, MD, of Dana-Farber Cancer Institute, was a randomized trial that compared the effectiveness of video visits with traditional genetic counseling among men diagnosed with prostate cancer.2 The study reported high uptake by both groups: 88% of the eligible men in the traditional counseling group agreed to be tested, compared with 93% of those eligible in the video group. Testing completion rates were 99% in both groups, and initial survey results patients in both groups were equally satisfied with the process. Over 2 years, 604 patients were tested and pathogenic variants were identified in 79 patients (13.2%).

However, Hofstatter noted that ProGen took place in highly controlled setting—what would be the result in a study that reflected real-world conditions? For this answer, she turned to the MAGENTA study,3 which recruited many of its participants over social media. The study aimed to learn whether pre- and post-test genetic counseling is needed to best guide genetic testing for women at risk of hereditary breast and ovarian cancer. All counseling took place online. Of 3822 patients randomized, 3111 were placed in a family history cohort and 711 in a cascade cohort, where someone in the family was known to have a mutation. Among those completing genetic testing, 173 participants or 7.2% had a mutation in a breast or ovarian gene, with 114 (5.7%) of the family history cohort and 59 (14.2%) of the cascade cohort.

Hofstatter explained the results, which focused on distress level among patients: it was lowest among those who had neither pre- nor post-test counseling. Overall, 318 participants (18%) had high levels of distress, without much different whether their test was positive or negative.

Both studies, she said, “demonstrate high uptake rates with pretest video education and truly represent new models of genetic counseling, breaking down barriers and improving accessibility to testing. And it would be very tempting to have our major take home message being that pretest counseling is really, ‘Less is more,’ or at least ‘It’s just as good.’” Let’s get rid of the people altogether.”

However, “Test completion or uptake of testing cannot be our only goal,” she said. “Truly It's what you do with the information from testing that counts. Certainly uptake, satisfaction, distress and intend to share are essential.”

PROMPT. For a look at how information is used, Hofstatter turned to the PROMPT study, which looked at how many women completed oophorectomy based on results of multi-panel genetic testing. While the results included some self-reported statements from the patients, the findings highlight concerns payers have had about genetic testing without proper counseling or education for providers: they may lead to unnecessary or even harmful procedures.

Of the 1566 women in the PROMPT registry who reported having oophorectomy, 487 (30.7%) reported having cancer treatment, 432 reported benign disease (27.6%) Another 186 (12.8%) reported pathogenic variants associated with risk of ovarian cancer. The majority of women had no family history of ovarian cancer, and most of the women having surgery were not yet 50 years of age. The study found that 10% to 15% of the women who had surgery had a pathogenic variant or a variant of unknown significance, and thus reported having a procedures without a clear indication.4

The study, Hofstatter said, “serves as a cautionary tale, especially when we're thinking about omitting or limiting the availability of genetic counseling as part of genetic testing.” Increased access to testing—a good goal—in combination with less counseling would invite “the inevitable potential for misinformation and possible mismanagement.”

A provider may have good intentions in streamlining the process, but Hofstatter said treatment management decisions “must be based on accurate risk assessment. And certainly, with less availability and less use of genetic counselors, the burden is going to be increasingly on the provider to make sure that they understand the implications of testing results.”


1. Stadler ZK, Maio A, Kemel Y, et al. Targeted therapy based on germline analysis of tumor-normal sequencing (MSK-IMPACT) in a pan-cancer population. J Clin Oncol 2020;38:(suppl; abstr 1500) DOI: 10.1200/JCO.2020.38.15_suppl.1500

2. Rana HQ, Stopfer JE, Petrucelli N, et al. A randomized controlled trial of video-education or in-person genetic counseling for men with prostate cancer (ProGen). J Clin Oncol. 2020;38:(suppl; abstr 1507) DOI: 10.1200/JCO.2020.38.15_suppl.1507

3. Swisher EM, Rayes N, Bowen D, et al. Results from MAGENTA: A national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk. J Clin Oncol 2020;38:(suppl; abstr 1506) DOI: 10.1200/JCO.2020.38.15_suppl.1506

4. Domchek SM, Brower J, Symecko H, et al. Uptake of oophorectomy in women with findings on multigene panel testing: Results from the Prospective Registry of Multiplex Testing (PROMPT). J Clin Oncol. 2020;38:(suppl; abstr 1508) DOI: 10.1200/JCO.2020.38.15_suppl.1508

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