Breast cancer phenotype in patients with hereditary gene mutations other than BRCA1 and BRCA2.

Abstract

e13121 Background: Use of multi-gene panel (MGP) testing for hereditary breast cancer (BC) has increased significantly. Unlike in case of TNBC diagnosed before age 60 and ordering BRCA testing; for MGP testing, healthcare providers depend on personal and/or family history of cancer as tumor phenotype and on patient characteristics for non-BRCA hereditary BC genes which are not well described. Therefore, we planned to evaluate tumor phenotype of BCs associated with hereditary gene mutations other than BRCA 1 and BRCA2. Methods: Consecutive patients with invasive BC who are in a prospective cohort study and who underwent MGP testing based on published criteria as clinically indicated were included in the study. All patients’ breast pathology slides were reviewed by breast pathologists at our institution. For statistical analysis: Patients’ demographic and clinical characteristics were summarized using descriptive statistics such as frequency distribution, mean (± s.d.) and median (range). SAS version 9.4 and S-Plus version 8.04 were used to carry out the computations for all analyses. Institutional IRB approval was obtained. Results: Between 2013 and 2017, 1607 patients underwent MGP testing and 347 were found to be positive for a pathogenic variant. For the study purposes we included only patients with invasive breast cancer (N = 146). Median age was 45.1 yrs (Range: 25-78). Genetics testing results were as follows: BRCA1: 38 (26%), BRCA2: 37 (25%), CHEK2 15 (10%), PALB2: 12 (8%) , ATM: 12 (8%), TP53: 9 (6%), CDH1 : 5 (3%), PTEN: 3 (2%), BRIP1: 3 (2%), and 12 patients (8%) positive for other genes (CDKN2A, MUTYH, PMS2, APC, BARD1, MLH1, NBN, RAD51C, and SDHD). Tumor phenotype by gene mutation in shown in table 1. Conclusions: Several hereditary BC genes are associated with ER positive BC which could have implications for chemoprevention, while others associated with ER neg/TNBC that could have therapeutic implications. These findings and implications need to be further studied in larger cohorts. [Table: see text]