Clinical Guidelines for Germline Cancer Testing

Breast & Gynecologic Cancers

Individuals should be considered for genetic testing if they have:

  • Breast cancer at any age

  • Ashkenazi Jewish ancestry

  • Uterine/endometrial cancer ≥50y*

Genetic testing is recommended when there is a personal or family history†‡ of:

  • Breast cancer ≤50y†
  • Ovarian cancer (including peritoneal and fallopian tube)†
  • Multiple primary breast cancer diagnoses†
  • Triple-negative breast cancer (ER-, PR-, HER2-)†
  • Male breast cancer†
  • Pancreatic cancer‡
  • Metastatic or high-risk prostate cancer‡
  • Uterine/endometrial or colorectal cancer <50y‡
  • A known pathogenic/likely pathogenic variant (mutation) of a cancer susceptibility gene in a blood relative

*In individuals untested for MMR deficiency status in tumor or with absence of MMR deficiency in tumor
†Eligible relatives include first-degree (parent, sibling, child) and second-degree (grandparent, grandchild, aunt, uncle, niece, nephew, half-sibling)
‡Eligible relatives include first-degree (parent, sibling, child)

Criteria listed are not comprehensive. See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for complete testing criteria (NCCN.org).

 

Gastrointestinal Cancers & Polyps

Individuals should be considered for genetic testing if they have:

  • Colorectal cancer ≥50y*
  • 10-19 cumulative adenomas

Genetic testing is recommended when there is a personal history of:

  • Any Lynch syndrome-related† cancer <50y
  • Two Lynch syndrome-related† cancers in the same person
  • Mismatch repair (MMR) deficiency and/or abnormal IHC in a tumor
  • >20 cumulative adenomas
  • Diffuse gastric cancer (DGC) at any age
  • A known pathogenic/likely pathogenic variant (mutation) of a cancer susceptibility gene in a blood relative

Genetic testing is recommended when there is a personal or family history‡ of:

  • Pancreatic cancer (exocrine)‡
  • ≥3 close relatives§ with Lynch syndrome-related† cancers
  • Colorectal or uterine/endometrial cancer <50y‡
  • Colorectal cancer or uterine/endometrial cancer and another Lynch syndrome-related† cancer in the same person‡

*In individuals untested for MMR deficiency status in tumor or with absence of MMR deficiency in tumor
†Lynch syndrome cancers may include: colorectal, uterine/endometrial, gastric, ovarian, pancreas, urothelial, brain (usually glioblastoma), biliary tract, and small intestine, as well as sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas.
‡Eligible relatives include first-degree (parent, sibling, child)
§Eligible relatives include first-degree (parent, sibling, child) and second-degree (grandparent, grandchild, aunt, uncle, niece, nephew, half-sibling)

Criteria listed are not comprehensive. See NCCN Guidelines® for complete testing criteria (NCCN.org).

 

Prostate Cancers

Individuals should be considered for genetic testing if they have::

  • Prostate cancer ≤55y
  • Intermediate risk* prostate cancer with intraductal/cribriform histology

Genetic testing is recommended when there is a personal or family history* of:

  • Metastatic, node-positive, high- or very high-risk‡ prostate cancer
  • Prostate cancer and a relative§ with one of the following cancers:
    • Breast cancer ≤50y
    • Ovarian cancer
    • Pancreatic cancer
    • Male breast cancer
    • Metastatic, node-positive, high- or very high-risk‡ prostate cancer
  • Prostate cancer and Ashkenazi Jewish ancestry
  • A known pathogenic/likely pathogenic variant (mutation) of a cancer susceptibility gene in a blood relative

*Defined as having one or more of the following: Grade Group 2 or 3 (Gleason score 7), clinical stage T2b-T2c, and PSA 10-20 ng/m
†Eligible relatives include first-degree (parent, sibling, child)
‡Defined as Gleason score ≥8, or Grade Group of 4 or 5, or a prostate cancer that has grown outside of the prostate (clinical stage T3-T4), or a PSA level of more than 20ng/mL
§Eligible relatives include first-degree (parent, sibling, child), second-degree (grandparent, grandchild, aunt, uncle, niece, nephew, half-sibling) and third-degree (cousin, great-grandparent)

Criteria listed are not comprehensive. See NCCN Guidelines® for complete testing criteria (NCCN.org).

References:

  • Manahan ER, et al. Consensus Guidelines on Genetic Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019 Oct;26(10):3025-3031.
     
  • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate V.2.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed November 7, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
     
  • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed October 31, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.