Data show ‘critical need’ for universal genetic testing of patients with breast cancer
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Universal germline genetic testing benefited patients with breast cancer and their physicians in implementing effective precision treatments and personalized disease management, according to study results published in JAMA Network Open.
Background and methods
“This research stemmed from the question of how effective National Comprehensive Cancer Network guidelines’ restrictive criteria are at predicting which patients with breast cancer have pathogenic germline variants,” Edward D. Esplin, MD, PhD, FACMG, FACP, clinical geneticist at Invitae, told Healio. “Our previous prospective, observational, universal germline testing study, published in Journal of Clinical Oncology, of almost 1,000 patients found no statistically significant difference in the rate of pathogenic germline variants between patients with breast cancer who met NCCN criteria vs. those who did not meet the criteria. Results of that study also showed nearly half of patients with breast cancer who have a pathogenic germline variant are missed by NCCN guidelines. This landmark 2018 publication led the American Society of Breast Surgeons to issue new guidelines recommending universal germline genetic testing for patients with a current or past diagnosis of breast cancer.”
Certain medical centers implemented the guidelines; however, the clinical utility of universal germline genetic testing in patients with breast cancer remained unclear, Esplin continued.
“This prompted the current longitudinal outcomes analysis of the same cohort reported in 2018, demonstrating the clinical utility of universal genetic testing in patients with breast cancer,” he said.
The analysis included 952 patients aged between 18 and 90 years with a new and/or previous diagnosis of breast cancer who had not previously undergone genetic testing. Patients underwent assessment as “in-criteria” or “out-of-criteria” according to the guidelines and received testing with a multigene germline panel between 2017 and 2018.
Researchers determined the association between the prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features. They additionally assessed disease management recommendations that changed as a result of genetic testing results.
Findings
Overall, clinician-reported recommendations were provided for 939 patients with breast cancer (mean age at initial diagnosis, 57.6 years; 99.7% women; 74.8% white).
One or more changes to clinical recommendations occurred for 83.8% of in-criteria patients, which included those who had pathogenic variants within the criteria of previous guidelines, and for 67.6% of out-of-criteria patients, which included those who did not meet testing criteria under previous nonuniversal guidelines but had a pathogenic or likely pathogenic variant in a cancer predisposition gene.
Results showed recommendations changed as a result of genetic testing results specifically for 63.6% out-of-criteria patients with a variant in a breast cancer predisposition gene.
“We also found that the BRCAPRO statistical model was inadequate for predicting the likelihood of patients with breast cancer having a pathogenic variant in clinically actionable high-risk genes outside of BRCA1 or BRCA2,” Esplin said. “Physicians also reported germline genetic testing positively impacted health outcomes for two-thirds of patients with pathogenic variants.”
Of note, no changes to clinical recommendations occurred for most patients with negative results (98.9%) or those with variants of uncertain significance (96.7%).
“This led to physicians considering genetic testing to be beneficial for one-third of patients with either negative or variants of uncertain significance results,” Esplin added.
Implications
The findings prove the clinical utility of universal germline genetic testing for all patients with a current or previous diagnosis of breast cancer and reinforce the American Society of Breast Surgeons guidelines establishing this as the standard of care, Esplin said.
“In the context of published research on the clinical utility of moderate-risk genes in breast cancer, and recent advances in [poly(ADP-ribose) polymerase inhibitor] therapy for patients with early breast cancer in the OlympiA trial, the data demonstrate the critical need for universal genetic testing to provide access to precision therapies and clinical treatment trials and establish management recommendations for patients with breast cancer, as well as cascade testing and precision prevention for their family members,” he continued.
Next steps should include systematic, nationwide implementation of standard of care universal germline testing for all patients with breast cancer, per the American Society of Breast Surgeons guidelines, Esplin added.
“Multiple institutions already implement universal genetic testing for breast cancer, such as the University of Southern California Norris Comprehensive Cancer Center, Mayo Clinic and Intermountain Healthcare, among others,” he said. “The sooner we systematically implement universal genetic testing for patients with breast cancer, the closer we’ll be to achieving President Joe Biden’s Cancer Moonshot 2.0 objectives of reducing cancer mortality and improving the lives of patients with cancer and their families.”
References :
- Beitsch PD, et al. J Clin Oncol. 2019;doi:10.1200/JCO.18.01631.
- Clinical practice guidelines recommend genetic testing of all patients with breast cancer (press release). Available at: ir.invitae.com/news-and-events/press-releases/press-release-details/2022/Clinical-Practice-Guidelines-Recommend-Genetic-Testing-of-All-Patients-with-Breast-Cancer/default.aspx. Published Sept. 22, 2022. Accessed Oct. 7, 2022.
- Manahan ER, et al. Ann Surg Oncol. 2019;doi:10.1245/s10434-019-07549-8.
- Whitworth PW, et al. JAMA Netw Open. 2022;doi:10.1001/jamanetworkopen.2022.32787.
For more information:
Edward D. Esplin, MD, PhD, FACMG, FACP, can be reached at ed.esplin@invitae.com.
Perspective
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Julia A. Smith, MD, PhD
We are strong believers in universal genetic testing.
This paper, as have numerous others, makes clear that it is no longer sufficient to rely entirely on the clinical judgment of health care providers, including genetic counselors. They consistently miss identifying a significant number of genetic mutations that would be clinically actionable.
The push for universal genetic testing is certainly worthwhile and the more we do, the more we learn about what else we can do.
Germline genetics have opened the way to predictive and prognostic understanding of cancer, as well as treatment and screening.
Hopefully after this generation, and likely after the next, we will be able to sequence children’s genomes at birth to design screening and prevention for their lifetime.
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