Abstract PO1-09-03: Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes
Authors: Miller Devon , Pritzl Stephanie , Tess Angela , Gooding Jessica , Barroilhet Lisa , Dubenske Lori , Wisinski Kari 
Published: May 2024

Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population.

Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-03.