Abstract P3-08-04: Trends in age of breast cancer diagnosis for women with pathogenic variants in genes associated with increased breast cancer risk
Authors: Gorringe H , Rosenthal E , Kidd J , Brown K , Manley S 
Published: March 2017

Abstract
Background: The National Comprehensive Cancer Network (NCCN) currently recommends consideration of genetic testing for appropriate, high risk individuals when it will impact medical management of the individual or at-risk family members. Established NCCN testing criteria are based on family history, the presence of multiple primary cancers, and age of diagnosis. For breast cancer, women diagnosed before age 50 are eligible for genetic testing with limited family history; however, these criteria were developed based on high-risk breast cancer genes, such as BRCA1 and BRCA2. The growing use of gene panels has extended testing to include genes associated with a 2- to 4-fold increased risk for breast cancer. Although NCCN guidelines now include medical management recommendations for these genes, it is unclear whether current criteria appropriately identify candidates for testing who have pathogenic variants (PVs) in genes with moderate breast cancer risk. Here, we investigated the age of breast cancer diagnosis in women carrying PVs in genes with high or moderate breast cancer risk.
Methods: Clinical testing was performed for 68,239 women with a personal diagnosis of breast cancer using a 25-gene hereditary cancer panel that includes genes with a high (BRCA1, BRCA2, PTEN, TP53) or moderate (PALB2, CHEK2, ATM, STK11, CDH1, NBN, BARD1) risk of breast cancer. The majority of women tested met current NCCN criteria for testing based on their personal and/or family cancer history. The proportion of women with a PV who were diagnosed &lt;50 and &lt;60 years of age was evaluated.
Results: Overall, 5,231 women diagnosed with breast cancer were found to carry a PV in a gene with high or moderate breast cancer risk. 70.2% of women with PVs in genes with a high breast cancer risk were diagnosed with breast cancer before age 50, compared to only 55.5% of patients with PVs in genes with moderate breast cancer risk (see Table). However, similar proportions of women with PVs in genes with a high (89.3%) and moderate (80.2%) breast cancer risk were diagnosed before age 60 (see Table).
GeneDiagnosed &lt;50Diagnosed &lt;60Moderate Breast Cancer RiskCHEK2458 (59.3%)629 (81.5%)PALB2337 (54.7%)507 (82.3%)ATM315 (52.4%)452 (75.2%)BARD168 (51.5%)111 (84.1%)NBN56 (52.3%)86 (80.4%)CDH124 (58.5%)33 (80.5%)STK114 (66.7%)6 (100%)Total1262 (55.5%)1824 (80.2%)High Breast Cancer RiskBRCA11086 (76.4%)1314 (92.4%)BRCA2901 (63.0%)1227 (85.8%)TP5361 (83.6%)68 (93.2%)PTEN28 (90.3%)31 (100%)Total2076 (70.2%)2640 (89.3%)
Conclusions: Approximately half of the women with a PV in a moderate breast cancer risk gene identified here were diagnosed before age 50. This likely overestimates the proportion of moderate-risk PV carriers with early onset breast cancers, as current testing criteria are weighted towards diagnoses at young ages. Given that there are now medical management guidelines for patients who carry PVs in most of the moderate-risk breast cancer genes, it is important to consider whether current testing criteria developed for genes with a high breast cancer risk effectively identify women with PVs in moderate-risk genes.
Citation Format: Gorringe H, Rosenthal E, Kidd J, Brown K, Manley S. Trends in age of breast cancer diagnosis for women with pathogenic variants in genes associated with increased breast cancer risk [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-04.