Abstract
The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.
Highlights
Introduction recent introduction of multigene panel testing for mutations associated with The introduction ofraised multigene testinginfor mutations associated with breast breast and/orrecent ovarian cancer has newpanel challenges the management of both indiand/or ovarian cancer has raised new challenges in the management of both individuals viduals at increased cancer risk and cancer patients
In a recent retrospective case-control study, Bergstrom and colleagues [17] found that BC patients with germline pathogenic variants of ATM, CHEK2, or PALB2 have an increased family history of breast cancer, tumor size >2.0 cm at the time of diagnosis, and potentially an increased risk of recurrence compared to mutation-negative patients
The ATM and CHEK2 genes encode proteins that act as tumor suppressors and are involved in the DNA damage response following generation of DNA double-strand breaks (DSBs) [4]
Summary
Introduction recent introduction of multigene panel testing for mutations associated with The introduction ofraised multigene testinginfor mutations associated with breast breast and/orrecent ovarian cancer has newpanel challenges the management of both indiand/or ovarian cancer has raised new challenges in the management of both individuals viduals at increased cancer risk and cancer patients. BRCA1/2 mutations, other high/moderate-penetrance genes mutations, pathogenic other high/moderate-penetrance genes canBRCA1/2 increase the risk of breast and/orvariants ovarianin cancer. While providing riskcan increase the risk of breast and/or ovarian cancer. For CHEK2 1.08% in unselected breast cancer patients, whereas the prevalence in unafandwomen for CHEK2. CHEK2 sidered as moderate-penetrance genes and are involved in DNA-double strand break re- are considered as moderate-penetrance genes and are involved in DNA-double strand pair mechanisms [4]. The ATM protein kinase is a critical intermediary inbreak a repairofmechanisms [4]. Intoparticular, the ATM protein kinaseother is a critical intermediary number cellular responses ionizing irradiation and possibly stresses. After DNA damage, ATM and DNA-dependent (DNA-PK) protein kinase of the cell cycle [5]. Mitosis [6] (Figure 1)
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