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. 2021 Apr 21;12(5):616.
doi: 10.3390/genes12050616.

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

Angela Toss  1   2 , Elena Tenedini  3 , Claudia Piombino  1 , Marta Venturelli  1 , Isabella Marchi  1 , Elisa Gasparini  4 , Elena Barbieri  1 , Elisabetta Razzaboni  5 , Federica Domati  1   3 , Federica Caggia  1   3 , Giovanni Grandi  3   6 , Francesca Combi  7   8 , Giovanni Tazzioli  3   8 , Massimo Dominici  1   3 , Enrico Tagliafico  3   9   10 , Laura Cortesi  1
Affiliations

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

Angela Toss et al. Genes (Basel). .

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.

Keywords: ATM; CHEK2; bilateral tumor; breast cancer; genetic testing; mastectomy.

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Conflict of interest statement

The authors declare no conflict of interest associated with this manuscript.

Figures

Figure 1
Figure 1
Role of ATM and CHK2 in the pathways of cell cycle arrest, apoptosis, DNA repair and mitosis. In particular, the MRN complex resects DNA at the double-strand break (DSB) and recruits ATM that phosphorylates CHK2 and recruits the BRCA complex.
Figure 2
Figure 2
Study flow-chart.
See this image and copyright information in PMC

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