ASCO 2020: Genetic Testing

July 22, 2020
Mary Caffrey, Peter Wehrwein

Allison Inserro

Evidence-Based Oncology, July 2020, Volume 26, Issue 6

Four studies were highlighted that amplified 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 unnecessary surgeries.

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

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 of the 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 the virtual session, “Cancer Risk, Genetics, and Prevention,” held May 30 during the¢American Society of Clinical Oncology (ASCO) 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 unnecessary surgeries.

MSK-IMPACT TRIAL. Tumor tests typically look for acquired mutations—somatic testing—to select targeted therapies. MSK-IMPACT evaluated the value, or clinical utility, of adding germline profi ling, for inherited mutations, for patients with advanced cancer, through next-generation sequencing.1 From a study population of 11,975 patients, investigators 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 (n = 416) or for Lynch syndrome (n = 149). Of importance, Hofstatter said, is the share of patients with advanced disease who received a targeted therapy: The authors reported the share was 45.3% 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 signifi cantly over time,” Hofstatter noted. Increasingly, she said, 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 reminded.

IMPROVING ACCESS. Despite broader availability of germline testing, uptake is poor. For instance, only about 2% of Lynch syndrome carriers have been identifi ed, Hofstatter said. Lack of knowledge, cost, inconvenience, and a shortage of genetic counselors—some payers require a counseling 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 coronavirus 2019 pandemic. The ProGen study, led by Huma Q. Rana, MD, of Dana-Farber Cancer Institute, was a randomized trial that compared the eff ectiveness 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 who agreed to be tested, and according to 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 of them (13.2%).

However, Hofstatter noted that ProGen took place in a highly controlled setting. What, she wondered, 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 posttest 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 (7.2%) had a mutation in a breast or ovarian gene;

this included 114 patients (5.7%) in the family history cohort and 59 (14.2%) in the cascade cohort. Hofstatter explained the results, which focused on distress level among patients: It was lowest among those who had neither pre- nor posttest counseling. Overall, 318 participants (18%) had high levels of distress, and there was little difference whether their test was ultimately positive or negative.

Both studies, Hofstatter said, “demonstrate high uptake rates with pretest video education, and they truly represent new models of genetic counseling, breaking down barriers and improving accessibility to testing.

“And it would be very tempting,” Hofstatter continued, “to have our major take-home message being that pretest counseling is really [superfluous]—

that ‘Less is more,’ or at least that no counseling ‘is just as good.’ [Some could say,] ‘Let’s get rid of the counselors] 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 intention-to-share are essential.”

PROMPT TRIAL. For a view of how information is used, Hofstatter turned to the PROMPT study, which examined how many women completed oophorectomy based on results of multipanel genetic testing. While the results included some self-reported statements from the patients, the findings highlight the concerns payers have had about genetic testing without proper counseling or education for providers: The testing 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 and 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 aged 50 years. The study found that 10% to 15% of the women who had surgery had a pathogenic variant or a variant of unknown signifi cance, and thus were reporting having a procedure 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.Š2020;38(15 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(15 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.Š2020;38(15 suppl; abstr 1506). doi:10.1200/


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(15 suppl; abstr 1508). doi:10.1200/JCO.2020.38.15_suppl.1508

MD Anderson’s Lu: MAGENTA Highlights Need to Use Genetic Counselors in "Most Effective Way Possible"

Women who undergo genetic testing for hereditary breast and ovarian cancer are often advised to speak with a genetic counselor before and after they take the test, even if the result is ultimately negative for a mutation that would indicate a greater risk.

But results presented virtually at the 2020 annual meeting of the American Society of Clinical Oncology suggest that an online educational video about genetic testing may be suffi cient, and that women often don’t need to speak in person with a genetic counselor in the context of this type of testing. “We were surprised by the findings,” said Karen H. Lu, MD, the study’s principal investigator and chair of the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center, in an interview.

“I would hate for anyone to say, ‘We don’t need genetic counselors—they are not necessary,’” Lu added. “I think what [we] need to do is use them in the most effective way possible.”

Lu and her colleagues presented findings from MAGENTA (Making GENetic Testing Accessible), a 4-arm study that included 3111 women with a family history of hereditary breast and ovarian cancer and another group of 711 women with a family member whose genetic test results were positive for a risk-conferring mutation. Women enrolled in the trial watched an online educational video about genetic testing. Lu explained that women in the control arm of the study then spoke with a genetic counselor by telephone before and after they took the genetic test, which was an at-home “spit kit” test that involves collecting saliva sample for DNA testing. (The MAGENTA study website describes it as “the study of genetic testing from your living room.”)

Others arms of the study included genetic counseling only before the genetic test, only after, and no genetic counseling either before or after.

However, if the test came back positive for a risk-conferring mutation, genetic counseling was given regardless of which arm of the study the woman was in. Among the participants who completed testing, 173 (7.2%) had a positive test.

The primary outcome was “cancer risk distress” at 3 months. Lu and her colleagues measured distress among the women in 3 groups with more limited genetic counseling—including the group that didn’t receive any counseling if their results were negative. These results were noninferior to those of the group that received counseling before and after the test, the scenario which Lu described as the current standard of care. Analysis of data on secondary end points such as anxiety, depression and “decisional regret” painted a similar picture of no difference among the 4 arms. However, test completion was highest in the no-counseling arm (86.4%) and lowest in the control arm (60.6%).

Lu said genetic counselors provide “a wonderful service” to patients, but she added that there aren’t enough of them, particularly as testing becomes more prevalent and the results become more instrumental in making treatment decisions. She said the most effective way to use counselors may be to focus their efforts on people who test positive for risk-conferring mutations and those with a strong family history of cancer.

The overarching concern is making genetic testing more accessible, so women at high risk are identified and monitored or treated early, said Lu. “As a whole, [the results] really show that this type of testing—which is available commercially—can be used,” she said.

Study Shows How NGS, Precision Medicine Benefited Patients at Community Cancer Clinic

In oncology, precision medicine is already well established, with targeted therapies approved based on the patient’s genetic makeup or genetic variants of their tumor. Now, a combination of precision medicine, next-generation sequencing (NGS), and diagnostics is making its way into community cancer clinics. Study outcomes revealed during the American Society of Clinical Oncology 2020 Virtual Scientifi c Program analyzed NGS testing results in a community cancer care clinic in coordination with a precision medicine program.

With decreasing costs—of NGS to identify both germline and somatic pathogenic variants, and of other technological advancements—there is a critical need for curation and interpretation of these results, the study authors noted, as clinicians often order the tests simultaneously.

The retrospective review examined germline NGS results from patients who were seen since 2001 by the Hereditary Cancer Program at Hoag Family Cancer Institute in Newport Beach, California. Researchers also compared those who had both positive genetic testing results for germline and somatic variants and those who had tumor molecular profiling. The cancer program saw a total of 8239 patients; of those, 6100 had germline testing done, and approximately 50% had multigene panel testing (MGPT).

Results showed that 15% of the patients with germline testing had a pathogenic or likely pathogenic mutation. Of those patients with positive results, 71% had breast or ovarian cancer, while 29% had other cancer types.

The researchers also analyzed NGS results for 713 tumors tested in 1 year through a commercial laboratory. All cases were subject to the authors’ secondary annotation. That analysis resulted in additional recommendations in 40% of cases, beyond what was in the commercial report. The secondary annotations also provided additional clinical trial options in 30% of cases.

The cancer clinic had also begun a new program in the past year that led to the researchers examining tumor profi ling results for indications of possible germline mutations. By analyzing those results, the authors said they made recommendations for genetic counseling in 91 cases (12.8%). The results show the importance of genetic counseling and MGPT in a community setting in patients with personal and/or family histories of cancer, the authors wrote.

Physicians at the center have an increased understanding of the clinical utility of molecular testing, which benefi ts patients, the authors said.


Darabi S, Braxton DR, Homer J, et al.ŠPrecision medicine, genetics and genomics in a community cancer clinic. J Clin Oncol. 2020;38(15 suppl; abstr e13511). doi:10.1200/JCO.2020.38.15_suppl.e13511