Abstract P2-09-05: Multiple-gene panel sequencing prompts no change in care compared to BRCA1 and BRCA2 testing in male breast cancer patients and their families
Authors: Fostira F , Saloustros E , Konstantopoulou I , Tryfonopoulos D , Barbounis V , Mauroudis D , Georgoulias V , Fountzilas G , Yannoukakos D 
Published: May 2016

Abstract
Male breast cancer is a rare cancer entity, representing just 1% of all cancers diagnosed in men. It shares clinical and biological characteristics with post-menopausal female breast cancer, although recent reports showed that they are not identical. Approximately 10% of unselected male breast cancer cases carry BRCA1 & BRCA2 mutations, with the most frequently mutated gene being BRCA2. Multiple-gene sequencing has already entered clinical practice and leads in detection of potential pathogenic variants in other cancer predisposition genes, in as many as 15% female breast cancer patients without BRCA1 & BRCA2 mutations. We evaluated the performance of a customized panel for cancer risk assessment in a representative sample of male breast cancer patients.
Ninety eight male individuals diagnosed with breast cancer (mean age 59y, range 38y-81y) and referred for genetic counseling between 2010 and 2015 were invited to donate a research blood sample. Patients were eligible irrespectively of family history and age at diagnosis. Genomic DNAs were used to prepare libraries for the capture of the entire coding regions of twenty six known -or suspected- breast cancer genes. These were: BRCA1, BRCA2, TP53, STK11, CDH1, PTEN, PALB2, ATM, CHEK2, NBN, BRIP1, BARD1, RAD51C, RAD51D, RAD50, BLM, SLX4, MRE11A, FAM175A, MLH1, MSH2, EPCAM, MHS6, PMS2, MUTYH, NF1.
Loss-of-function mutations have been found in three genes; BRCA2, BRCA1 and PMS2. Not surprisingly, the most frequently mutated gene was BRCA2 accounting for 5% of the cases, while BRCA1 and PMS2 mutations have been detected in single cases, accounting each for 1%. Interestingly, no mutations were identified in any of other genes that have been reported in female breast-ovarian cancer families (PALB2, TP53, ATM, CDH1, RAD51C, RAD51D, etc). Compared to BRCA1 & BRCA2 testing, gene panel prompted consideration of change in care (early colon cancer screening) in a single family (1%).
This is the first evaluation of the performance a multiple-gene panel in male patients with breast cancer. Our findings confirm that genetic counseling and BRCA1 & BRCA2 should be the primary concern for these patients and their families. Mutations in other genes been reported in female breast-ovarian cancer families were not identified in this cohort. If larger studies confirm our results, then multiple-gene sequencing panels may be of limited benefit for male breast cancer patients and their families.
Citation Format: Fostira F, Saloustros E, Konstantopoulou I, Tryfonopoulos D, Barbounis V, Mauroudis D, Georgoulias V, Fountzilas G, Yannoukakos D. Multiple-gene panel sequencing prompts no change in care compared to BRCA1 and BRCA2 testing in male breast cancer patients and their families. [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 P2-09-05.