Abstract P5-09-01: Racial/ethnic differences in BRCA1/2 and multigene panel testing among young breast cancer patients
Authors: Trivedi MS , Jones T , Jiang X , Underhill ML , Bose S , Silverman T , Chung WK , Kukafka R , Crew KD 
Published: May 2019

Background: Breast cancer (BC) patients diagnosed at age 50 and under are recommended to have germline genetic testing for hereditary BC due to a high likelihood of carrying a pathogenic mutation in a moderate or high penetrance risk gene. Completion of genetic testing among racial/ethnic minorities, particularly multigene panel testing, is understudied. We examined predictors of completion of BRCA1/2 and multigene panel testing among women with early onset BC and assessed racial/ethnic differences in genetic testing completion and results.

Methods: We performed a retrospective cohort study of 1370 BC patients diagnosed at &lt;50 years of age at Columbia University Medical Center (CUMC) from January 2007-December 2016.Data on socio-demographics, clinical factors, and genetic testing completion and results were collected from the medical record. We conducted descriptive statistics and univariate and multivariable logistic regression models.

Results: Our study population had a median age of 44 years (range, 19-50); 44% non-Hispanic white, 24% Hispanic, 13% non-Hispanic black, 10% Asian, 9% other; 61% private insurance, 22% Medicaid, 17% other. Nearly half of the women (N=607; 44.3%) had genetic testing performed. In the multivariable regression model, genetic testing completion was less likely with increasing age at diagnosis (odds ratio [OR]=0.93; 95% confidence interval [CI]=0.91-0.95) and stage 0 or 4 BC compared to stage 1 (OR=0.67; 95% CI=0.46-0.97 and OR=0.35; 95% CI=0.19-0.64, respectively). Completion of genetic testing was more likely with a family history of BC (OR=5.55; 95% CI=3.92-7.87). Genetic testing completion did not vary by race/ethnicity or insurance coverage. Across all racial/ethnic groups, the frequency of pathogenic/likely pathogenic variants identified was 13.0% and 10.5% had at least 1 variant of uncertain significance (VUS). The highest VUS frequency was among Asians (21.2%). The percentage of women undergoing genetic testing increased over time from 18.5% in 2007 and reached a peak of 69.3% in 2015. From 2007 to 2016, the percentage of pathogenic/likely pathogenic variants detected increased from 3.4% to 9.1% and the VUS frequency rose from 3.4% to 13.3% with increasing use of panel testing.

Frequency of pathogenic variants and VUS among women ≤ 50 years diagnosed with BC at CUMC (2007-2016) Pathogenic variantsVUSTotal81 (5.9%)74 (5.4%)BRCA144 (3.2%)10 (0.7%)BRCA221 (1.5%)10 (0.7%)ATM3 (0.2%)9 (0.6%)CHEK23 (0.2%)8 (0.5%)Other variants detected in: APC, BARD1, BRIP1, CDH1, CDKN2A, MEN1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PHOX2B, PMS2, POLE, PTEN, RAD50, RAD51C, SDHA, STK11, TP53

Conclusions and Relevance: Nearly half of the women with early onset BC had genetic testing. We did not observe disparities in genetic testing by race/ethnicity or insurance coverage. Genetic testing completion, as well as the frequency of pathogenic/likely pathogenic variants and VUS detection, increased over time as panel testing replaced BRCA1/2 testing. Counseling on the likelihood of obtaining uncertain results should be provided to all patients undergoing hereditary BC genetic testing, particularly to racial/ethnic minorities.

Citation Format: Trivedi MS, Jones T, Jiang X, Underhill ML, Bose S, Silverman T, Chung WK, Kukafka R, Crew KD. Racial/ethnic differences in BRCA1/2 and multigene panel testing among young breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-01.