Selection of Germline Genetic Testing Panels in Patients with Cancer

Publication Date: May 17, 2024
Last Updated: May 17, 2024

Diagnosis

Family History Collection

 Recommendation 1.1

All patients should have a family history taken and recorded. (NR, S)
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Recommendation 1.2

  • Patients should be asked to provide the following information as part of this family history. Patients may not have complete information, but that should not be considered an impediment to asking these questions. Only information about biologic relatives is pertinent.
  • Does the patient know of any cancers in any first-degree biological relatives:
  • siblings, parents, children?
  • Does the patient know of any cancers in any second-degree biological relatives (on both maternal and paternal sides): grandparents, aunts, uncles, grandchildren, nieces, nephews, half siblings?
  • For each cancer in the family, ask for the following details: Type of primary cancer(s); age at cancer diagnosis for each primary cancer; were multiple cancers of one type involved (e.g., bilateral breast cancer or multiple colon cancer primaries)?
  • Does the patient know of any relative who has had germline genetic testing for cancer predisposition, and if so, what were the results?
  • What is the patient’s ethnicity?
(NR, S)
Qualifying statements:
  • The gender assigned at birth of biological relatives is important to the family history.
  • Where it is possible and time permits, information on third-degree relatives (e.g., cousins), consanguinity, and personal and family history of colon polyps can help inform genetic testing and counseling, especially with interpretation of results.
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Germline Multi-gene Panel Testing

Recommendation 2.1

When germline genetic testing is indicated for a patient with cancer, multi-gene panel testing should be offered if more than one gene is relevant (See Table 1 for details). (NR, S)
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Recommendation 2.2

When considering what to order for multi-gene panel testing, clinicians should apply the following principles:
  1. The minimal panel should include at least the more strongly recommended genes for that patient based on the patient’s personal and family history of cancer from Table 1 of this guideline and may include the less strongly recommended genes.
  2. A broader panel may be ordered when the potential benefits of such a panel can be clearly identified.
  3. When ordering a panel (especially a broader panel), the clinician should ensure that potential harms are mitigated. See Clinical Interpretation for further clarification.

A smaller panel of genes may be tested initially when results are needed quickly for treatment decision making with subsequent expansion to a larger panel of genes. (NR, NR)
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Germline Multi-gene Panel Testing

Recommendation 3

If germline multi-gene panel testing is offered, testing for pathogenic variants in the genes in Table 1 is recommended for the indicated populations of patients with cancer. Testing the genes in the left-hand column is more strongly recommended based on the higher relative risk for that cancer and/or higher actionability than those on the right but testing all genes relevant to the patient personal and family cancer history is reasonable. See text for criteria for the column assignments. (NR, S)
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Genes to be Included in Multi-gene Panels

 Recommendation 4.1

Patients who meet criteria for germline genetic testing should be offered that testing regardless of results from tumor testing (i.e., genomic profiling from tumor biopsy or circulating tumor DNA testing). (L, S)
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Recommendation 4.2

Regardless of germline genetic testing criteria, when a pathogenic variant is identified with tumor testing in a gene listed in Table 2 germline genetic testing should be offered according to the criteria in Table 2 and Table 3. (M, S)
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Selection of Germline Genetic Testing Panels in Patients with Cancer

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

May 17, 2024

Last Updated Month/Year

November 22, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

The purpose of this guideline is to aid oncologists in (1) identifying the components of family history most relevant to germline testing, (2) understanding the potential benefits and harms of ordering multigene panels, (3) identifying the most relevant cancer susceptibility genes to include in a germline multigene panel on the basis of a patient's personal and family history of cancer, and (4) understanding when germline genetic testing is indicated for patients who have had tumor genomic profiling.

Target Patient Population

Adult patients with selected cancers, excluding hematologic malignancies.

PICO Questions

  1. What is the importance of family history collection in the setting of germline multigene panel testing and what elements of family history are most important?

  2. When and how should multigene panel germline testing be used when germline genetic testing is indicated?

  3. Which genes are generally recommended for germline genetic testing for patients with selected cancers?

  4. Which patients should be offered germline genetic testing who will have or have had somatic genetic tumor testing (ie, tumor genomic profiling)?

Inclusion Criteria

Male, Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis

Keywords

prostate cancer, colorectal cancer, melanoma, cutaneous melanoma, sarcoma, soft tissue sarcoma, Breast cancer, Endometrial cancer, Gastric cancer, Gastrointestinal stromal tumors , Medullary thyroid carcinoma, Non-small cell lung cancer, Adrenocortical tumors, Ovarian cancer , uveal melanoma, Pancreatic adenocarcinoma, Phaeochromocytomas, paragangliomas, Renal cell carcinoma, osteosarcoma

Source Citation

Tung N, Ricker C, Messersmith H, et al. Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline. J Clin Oncol. 2024 May 17. doi: JCO.24.00662

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
124
Literature Search Start Date
May 17, 2022
Literature Search End Date
June 1, 2023