Abstract P3-08-05: The yield of germline genetic testing in breast cancer patients diagnosed prior to age 50
Authors: Madlensky L , De Rosa D , Forbes K 
Published: March 2017

Abstract
Young breast cancer (BC) patients are more likely to carry a mutation in a cancer predisposition gene than women diagnosed later in life. Historically young BC patients were eligible for BRCA1/2 genetic testing, but now with the advent of larger panels, more extensive germline genetic testing is available. Little is known about the yield of panel testing in young BC patients. The goal of this study is to report on the testing outcomes of referrals to a single institution cancer genetics program for women who had a diagnosis of BC at or prior to age 50.
METHODS: Cases were identified from the cancer registry of a single institution. Women with invasive breast cancer or DCIS were included if their diagnosis was at or before age 50. Charts were reviewed to abstract data on age of diagnosis, type of testing offered, and results of genetic testing, as well as insurance status and family history of cancer.
RESULTS: A total of 386 young BC patients were referred for genetic counseling in 2011-2015. Of those, 287 (74%) attended a genetic counseling appointment. Many of the women not attending had previously had genetic testing with an outside provider; their test results were included in the table below. Of the 287 attending a genetics consultation, most were offered genetic testing (87.1%); most of those not offered testing had either already been tested but without genetic counseling, or did not meet current NCCN or their insurer's criteria for testing. Eighteen women were offered a panel but elected to have only BRCA testing due to concerns about variants of unknown significance (VUS). Of those tested, 15.4% had a pathogenic or likely pathogenic mutation identified. Of women who had only BRCA testing, 11.7% were positive and 4.4% had a VUS. Of those who had panel testing, 16.9% were positive and 19.3% had a VUS.
Percentage of women with positive tests by age at diagnosisAge at Dx30 or less31-3536-4041-4546-50Total (n=18)(n=39)(n=78)(n=109)(n=108)(n=352)BRCA1/227.8%18.0%16.7%6.4%6.5%11.1%Other genes11.1%5.1%3.8%4.6%2.8%4.3%Total yield38.9%23.1%20.5%11.0%9.3%15.4%
Other genes with positive panel results included 4 x TP53 mutations, 4 x CHEK2, 2 x PALB2 and 1x each of RAD51C, RAD51D, STK11, NF1, and PTEN. The three patients who tested positive for a hereditary cancer predisposition syndrome (STK11, NF1, and PTEN positive) had clinical features of their respective syndromes. The STK11 patient was previously known to have Peutz-Jeghers syndrome, while the NF1 and PTEN patients had subtler features of Neurofibromatosis type 1 and PTEN-Hamartoma Tumor Syndrome (Cowden Syndrome) respectively.
CONCLUSIONS: The yield of germline genetic testing in BC patients increases with younger age of diagnosis. Panel testing increases the yield of testing above that of BRCA1/2 alone, and enabled the formal diagnosis of a few individuals with hereditary cancer syndromes who did not have classic features of their syndromes. The VUS rate for panel testing remains significant, and some women elect to have BRCA1/2 testing only due to personal preference because of VUS rates. These data describing the yield of testing in BC patients diagnosed at a young age may be useful for genetic counseling of this patient population.
Citation Format: Madlensky L, De Rosa D, Forbes K. The yield of germline genetic testing in breast cancer patients diagnosed prior to age 50 [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 P3-08-05.