Abstract P2-09-26: Women without significant claus model breast cancer risks may warrant breast MRI when a pathogenic/likely-pathogenic variant (PV/LPV) is detected in a hereditary cancer moderate risk gene
Authors: Alvarado M , Tiller GE , Kershberg H , Solomon SR , Mullineaux L , Haque R 
Published: May 2016

Background: Hereditary cancer gene panel testing can assess breast cancer risk for women with significant family histories. The Claus risk model is another method to determine which women qualify for annual breast MRIs based on family history, and can be used for those with BRCA negative status or for those who do not qualify for BRCA testing. In July 2014, Kaiser Permanente Southern California, a large integrated health plan, began using hereditary cancer panels comprised of moderate and high-risk breast cancer genes (GeneDx). At the time of implementation, no clinical management guidelines existed for patients with PV/LPV in moderate risk genes. In March 2015, the National Comprehensive Cancer Network (NCCN) amended the Genetic/Familial High Risk Assessment Breast and Ovarian guidelines to include breast cancer surveillance for patients with PV/LPV in moderate risk genes including ATM, CHEK2 and PALB2.

Objective: To determine if the identification of PV/LPV in moderate risk genes versus Claus model calculation increases the number of women warranting breast MRI in a managed care setting.

Methods: We performed a retrospective query of our gene panel results from 6/2014 to 5/2015 to identify patients with ATM, CHEK2 and PALB2 PV/LPV. Personal and family histories were obtained from the test requisitions. Patients with personal histories of breast cancer were excluded from analysis. We calculated the lifetime breast cancer risk using the Claus model for all eligible female patients with a moderate risk gene PV/LPV. To calculate the risk, the Claus model included family history of breast cancer in first and second-degree relatives. A lifetime breast cancer risk of &gt;20% indicates "high" risk.

Results: A total of 19 female patients without breast cancer had a PV/LPV detected in a moderate risk gene (ATM, CHEK2, and PALB2. Claus model calculation was feasible in 12 patients. Of these 12, 4 had a PV/LPV in ATM, 6 in CHEK2 and 2 in PALB2. Only one out of these 12 women was identified with &gt;20% risk of breast cancer based on the Claus model, and was recommended a breast MRI.

A review of electronic medical records (EMR) notes to date (June 1, 2015) revealed that breast MRI was recommended for 10 of the 12 patients above, and completed in 6. MRI identified a suspicious breast lesion in one patient. Follow-up tests and lumpectomy revealed atypical ductal hyperplasia and she will be followed with annual MRI and mammogram. The remaining 2 of12 women had no mention of MRI in their EMR, and will be flagged for follow-up to determine MRI status.

Conclusions: Eleven out of 12 women with a PV/LVP in a moderate risk gene would not have been identified as having an increased breast cancer risk by the Claus model. In our small sample, utilization of a High/Moderate Risk Gene Panel identified more patients potentially warranting enhanced breast cancer surveillance with annual breast MRI than the Claus model. This finding suggests that the use of hereditary cancer gene panel testing may impact the medical management of women with a familial risk for breast cancer. Larger studies with outcome data are needed to determine optimal surveillance guidelines.

Citation Format: Alvarado M, Tiller GE, Kershberg H, Solomon SR, Mullineaux L, Haque R. Women without significant claus model breast cancer risks may warrant breast MRI when a pathogenic/likely-pathogenic variant (PV/LPV) is detected in a hereditary cancer moderate risk gene. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-26.