Indications for Germline Testing After Genomic Tumor Testing (CME)

Getting Started

The goal of genomic tumor testing is to identify biomarkers that have predictive (therapeutic) or prognostic significance for an active cancer. Some of the DNA variants detected through these tests that are relevant for therapeutic decisions can also be associated with hereditary cancer risks (e.g., BRCA1, BRCA2). Knowing when a hereditary variant is present can be helpful in identifying targeted treatments, informing about future cancer risks, and identifying when close relatives might be at risk. This module will help you interpret genomic tumor test results to determine when a patient should be further evaluated for hereditary (germline) risk. This module uses practice cases to facilitate learning-by-doing, discussion of in-depth topics, and additional resources for more detail.

To claim credit, please complete the following steps:

1. Take a short pre-assessment. Complete two questions.

2. Review the course materials. Launch a new window to view the course, and close the window when you have completed the activities to return to this page.

3. Take the course evaluation.

4. Take the post-assessment to receive credit. Complete the four multiple choice questions. You must get 3 of the 4 answers correct to claim credit.

5. Go to your dashboard to print or view your certificate.

CME Information & Disclosures

Jointly Provided by The Jackson Laboratory and the University of Connecticut School of Medicine Office of Community and Continuing Medical Education

Publication Date: February 25, 2022
Expiration Date: July 1, 2024

Learning objectives

• Determine when germline testing may be indicated 
• Recognize steps and resources to facilitate germline testing 

Target Audience
Oncologists and other cancer clinicians, including fellows, physician assistants and nurses.

Accreditation
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Connecticut School of Medicine and The Jackson Laboratory. The University of Connecticut School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The University of Connecticut School of Medicine designates this enduring material for a maximum of .5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Planners, Writers, and Reviewers

• Emily Edelman, MS, CGC – The Jackson Laboratory
• Hayley Dunnack, MS, RN, CMSRN, OCN – Hartford Cancer Center
• Therese Ingram, MA – The Jackson Laboratory
• Kate Reed, MPH, ScM, CGC – The Jackson Laboratory
• Kathryn Robinson, PhD, MHA/Ed, RN – University of Maine
• Jens Rueter, MD – The Jackson Laboratory
• Linda Steinmark, MS, LGC – The Jackson Laboratory
• Christine Walko, PharmD – Moffit Cancer Center

Conflict of Interest Policy
All faculty members participating in CME activities sponsored by the University of Connecticut School of Medicine are required to disclose to the program audience any actual or apparent conflict of interest related to the content of their presentations. Program planners have an obligation to resolve any actual conflicts of interest and share with the audience any safeguards put in place to prevent commercial bias from influencing the content. 

Disclosure
Unless otherwise noted, the program planners and faculty do not have a financial interest/arrangement or affiliation with any organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this course. The following disclosures are reported that could be perceived as a real or apparent conflict of interest in the education program: Emily Edelman and Kate Reed received salary support in 2020 from Pfizer Inc. through an unrestricted quality improvement grant that focuses on improving ascertainment of hereditary breast cancer, provided by the American Community Cancer Centers and Pfizer Independent Grants for Learning & Change. In their roles as a planners and content authors, Ms. Edelman and Ms. Reed recused themselves from all deliberations relating to content related to the commercial entity with which they have financial interest and were not responsible for reviewing for bias any related content. All educational material has been peer-reviewed by external reviewers to assess for bias.

The program discusses investigational and off-label use of drugs in general terms, as options that may be considered for patients with advanced cancer after standard of care options have been exhausted.

Commercial Support
There is no commercial support being received for this activity. This program is supported by educational grants from The Maine Cancer Foundation and Harold Alfond Foundation.

References

Bristol Myers Squibb. Opdivo® (nivolumab) highlights of prescribing information. Updated 7/2021. Retrieved 9/20/2021.

Clark DF, Maxwell KN, Powers J, et al. Identification and Confirmation of Potentially Actionable Germline Mutations in Tumor-Only Genomic Sequencing. JCO Precis Oncol. Published online Aug. 19, 2019.

DeLeonardis K, Hogan L, Cannistra SA, Rangachari D & Tung NJ. When Should Tumor Genomic Profiling Prompt Consideration of Germline Testing? J Oncol Pract. 2019;15(9):465-473.

Hartmann A, Zanardo L, Bocker-Edmonston T, et al. Frequent microsatellite instability in sporadic tumors of the upper urinary tract. Cancer Res. 2002;62(23):6796–6802.

Kojima Y, Ohtsuka K, Ishii S, et al. STK11 p.F354L Germline Mutation in a Case of Multiple Gastrointestinal Tumors. Case Rep Gastroenterol. 2020;14(3):547–553.

Laderian B, Mundi P, Fojo T, & Bates SE. Emerging Therapeutic Implications of STK11 Mutation: Case Series. Oncologist. 2020;25(9):733-737.

Latham A, Srinivasan P, Kemel Y, et al. Microsatellite instability is associated with the presence of Lynch syndrome pan-cancer. J Clin Oncol. 2019;37(4):286–295.

Li MM, Chao E, Esplin ED, et al. Points to consider for reporting of germline variation in patients undergoing tumor testing: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(7):1142-1148. 

Lim W, Hearle N, Shah B, et al. Further observations on LKB1/STK11 status and cancer risk in Peutz–Jeghers syndrome. Br J Cancer. 2003;89(2):308–313.

Lincoln SE, Nussbaum RL, Kurian AW, et al. Yield and Utility of Germline Testing following Tumor Sequencing in Patients with Cancer. JAMA Netw Open. 2020;3(10):e2019452.

Lindner AK, Schachtner G, Tulchiner G, et al. Lynch Syndrome: Its Impact on Urothelial Carcinoma. Int J Mol Sci. 2021;22(2):531.

Mandelker D, Zhang L, Kemel Y et al. Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. JAMA. 2017;318(9):825-835.

Mandelker D, Donoghue M, Talukdar S, et al. Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group. Ann Oncol. 2019;30(8):1221-1231.

Merck and Co., Inc. KEYTRUDA (pembrolizumab) highlights of prescribing information. Updated 3/2021. Accessed 9/20/21.

Miller DT, Lee K, Chung WK, et al. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1381–1390.

National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (version 1.2022). Published August 11, 2021. Accessed 9/20/21. 

National Comprehensive Cancer Network. Genetic/familial high-risk assessment: Colorectal (version 1.2021). Published May 11, 2021. Accessed 9/20/21. 

National Comprehensive Cancer Network. Bladder Cancer (version 4.2021). Published July 27, 2021. Accessed 9/20/21. 

National Comprehensive Cancer Network. Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer (version 3.2021). Published September 9, 2021. Accessed 9/20/21. 

National Comprehensive Cancer Network. Breast Cancer (version 8.2021). Published September 13, 2021. Accessed 9/20/21. 

Ngeow J, Heald B, Rybicki L, et al. Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps. Gastroenterology. 2013;144(7):1402-1409.

Robson ME, Bradbury AR, Arun B et al. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. JCO. 2015;33(31):3660-3667.

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Should you have technical questions or questions regarding the content of the activity, please email Clinical and Continuing Education at the Jackson Laboratory.

Disclaimer 

All information in Precision Oncology Online Education is provided for educational purposes only. This information is not a substitute for clinical guidance or the consultation of a medical professional. Always seek the advice of a qualified health professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in Precision Oncology Online Education. Reliance on any information in Precision Oncology Online Education is solely at your own risk. The Jackson Laboratory does not endorse or recommend any specific procedures, tests, products, services, health professionals or other information that may be found in Precision Oncology Online Education.