The following are presentations from the NSGC meeting in September, 2014.

Family history identifies only a small fraction of patients with a >20% Lifetime Breast Cancer Risk


  • Pathogenic mutations in the intermediate penetrance genes ATM, CHEK2 and PALB2 increase the lifetime risk of female breast cancer above the 20% threshold at which guidelines for modified medical management apply.
  • The vast majority of women in whom mutations in these genes are identified would not have been identified based on family history alone.
  • Inclusion of these 3 genes in a hereditary cancer gene panel increases the sensitivity of the testing by 63.9% over testing only for BRCA1 and BRCA2, and by 59.8% over testing only for BRCA1/BRCA2 plus TP53, PTEN, CDH1, and STK11.

Inclusion of the ATM/CHEK2/PALB2 on multi-gene panel increases the percentage of patients receiving clinically significant results over testing for BRCA1/BRCA2 and other high penetrance genes


Gene Female Breast Cancer Risk (to age 80) Other Cancer Risks Associated Recessive Condition
ATM 17%-52% Pancreatic Ataxia Telangiectasia (AT)
CHEK2 23%-48% Colorectal
Male Breast
PALB2 20%-40% Male Breast
Fanconi Anemia (FANCN)

* Citations supporting the cancer risks provided in this table are available at



  • 832 mutations were identified among patients who met the NCCN guidelines for BRCA1 and BRCA2 testing alone.

    • 14 mutations in genes not associated with breast or ovarian cancer (MUTYH, APC, CDKN2A and SMAD4)
    • 38 mutations in the MMR genes


  • 93 mutations were identified among patients who met the NCCN guidelines for Lynch syndrome testing alone.

    • 22 mutations in genes not associated with colon or endometrial cancer (ATM, BARD1, BRIP1, NBN, PALB2, RAD51C, RAD51D)
    • 6 mutations in BRCA1 and BRCA2

Presented By:

Eric Rosenthal, PhD, ScM

Praveen Kaushik, MS, CGC

Detection of Pathogenic Mutations in Moderate Penetrance Breast Cancer Genes Significantly Increases the Number of Patients Identified as Candidates for Increased Screening
Abstract Summary Available Here

Comparison of mutation detection in cancer-specific versus pan-cancer approaches to an at-risk population
Abstract Summary Available Here

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