Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

TLDR

Li‑Fraumeni syndrome is a highly penetrant cancer syndrome with a lifetime risk for multiple cancers, including soft‑tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors. The NCCN Guidelines assess pathogenic or likely pathogenic variants linked to breast, ovarian, and pancreatic cancer and recommend genetic testing, counseling, and management strategies, with a focus on BRCA‑related breast/ovarian cancer syndrome and Li‑Fraumeni syndrome. The guidelines outline the assessment of these variants and prescribe specific genetic testing, counseling, and management approaches for affected individuals. BRCA1/2 carriers experience markedly increased breast and ovarian cancer risk, necessitating intensive screening and preventive strategies, and also exhibit elevated prostate and pancreatic cancer risk.

Abstract

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.