Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers

Abstract

The most common breast cancer (BC) susceptibility genes beyond <i>BRCA1/2</i> are <i>ATM</i> and <i>CHEK2</i>. For the purpose of exploring the clinicopathologic characteristics of BC developed by <i>ATM</i> or <i>CHEK2</i> mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen <i>ATM</i> and 17 <i>CHEK2</i> mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in <i>ATM</i> (26.3%) and <i>CHEK2</i> mutation carriers (41.2%). While 64.3% of <i>CHEK2</i> tumors were luminal A-like, 56.2% of <i>ATM</i> tumors were luminal B-like/HER2-negative. Moreover, 21.4% of <i>CHEK2</i>-related invasive tumors showed a lobular histotype. About a quarter of all <i>ATM</i>-related BCs and a third of <i>CHEK2</i> BCs were in situ carcinomas and more than half of <i>ATM</i> and <i>CHEK2</i>-related BCs were diagnosed at stage I-II. Finally, 63.2% of <i>ATM</i> mutation carriers and 64.7% of <i>CHEK2</i> mutation carriers presented a positive BC family history. The biological and clinical characteristics of <i>ATM</i> and <i>CHEK2</i>-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with <i>ATM</i> and <i>CHEK2</i> mutation carriers at the first diagnosis of BC.