Abstract P5-09-06: Underdiagnosis of HBOC in breast cancer patients: Are genetic testing guidelines a tool or an obstacle?
Authors: Beitsch P , Whitworth P , Baron P , Rosen B , Compagnoni G , Simmons R , Smith LA , Holmes D , Brown E , Gold L , Clark P , Coomer C , Grady I , Barbosa K , Riley L , Kinney M , Lyons S , MacDonald H , Kahn S , Ruiz A , Patel R , Curcio L , Esplin E , Yang S 
Published: May 2019

Abstract
Background: Pathogenic genetic variants are estimated to occur in 10-15% of all breast cancer patients, with BRCA 1/2 accounting for 40-50% of pathogenic/likely pathogenic (P/LP) variants. However, it is estimated that &lt;30% of breast cancer patients harboring a BRCA 1/2 variant have been identified, with the percentage being much less for ˜20 other breast cancer associated genes. Reasons for this are multifactorial and include complicated and restrictive testing guidelines developed at a time when the cost of testing was high and guidelines for management were limited. Today, cost has plummeted and there are definitive management guidelines for a broader range of genes. We created a community based Registry to determine the incidence of P/LP variants in breast cancer patients who meet and who do not meet the NCCN 2017 genetic testing criteria.
Methods: An IRB-approved multicenter prospective registry was initiated with 20 community and academic sites experienced incancer genetic testing and counseling.
Eligibility criteria included patients with a breast cancer diagnosis who had not been previously tested. Consecutive patients aged 18-90 were consented and underwent an 80 gene panel test (Invitae –Multi-Cancer Panel). The non-inferiority study was powered to detect a difference in P/LP variant rate of 4 percentage points with statistical significance (p&lt;0.05, Fisher's exact test).
HIPAA compliant electronic case report forms collected information on patient diagnosis, test results, and physician recommendations made after test results were received.
Results: Over 1000 patients were enrolled and data from 910 subjects analyzed to date. 50.4% met NCCN criteria and 49.5% did not. Median age for the enrolled patients is 60.5 and ranged from 22-93. 56.0% of patients were recently diagnosed with breast cancer. 10.9% of patients had a history of a prior non breast cancer. Overall, 8.9% of patients had a pathogenicvariant. 9.6% of patients who met NCCN criteria with test results had a P/LP variant. 8.2% of patients who did not meet criteria had a P/LP variant. The difference of positive cases among the two groups is not statistically significant (P = 0.49)
4.9% of patients had pathogenic variants if only an 11 gene standard breast cancer panel was considered.
The spectrum of mutated genes varied between the two groups, with some overlap.
Conclusions:
There was no statistically significant difference in the number of pathogenic/likely pathogenic variants between those patients who met and those who did not meet NCCN guidelines. Expanded panel testing yields more medically actionable P/LP variants than testing BRCA 1/2 alone or breast cancer panels with 11 genes. This study demonstrates that there will be a significant number of patients with P/LP variants are missed if NCCN guidelines are required for genetic testing. Current NCCN guidelines for the genetic testing of breast cancer patients are an obstacle to identifying patients with P/LP variants and should be removed.
Universal BC Genetic Testing RegistryNCCN Criteria (910 patients analyzed)#/% who have P/LP variants#/% who do not have P/LP variantsPatients who meet guidelines44/459 (9.6%)415/459 (90.4%)Patients who do not meet guidelines37/451 (8.2%)414/451 (91.8%)
Citation Format: Beitsch P, Whitworth P, Baron P, Rosen B, Compagnoni G, Simmons R, Smith LA, Holmes D, Brown E, Gold L, Clark P, Coomer C, Grady I, Barbosa K, Riley L, Kinney M, Lyons S, MacDonald H, Kahn S, Ruiz A, Patel R, Curcio L, Esplin E, Yang S. Underdiagnosis of HBOC in breast cancer patients: Are genetic testing guidelines a tool or an obstacle? [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 P5-09-06.