ATMgermline variants and male breast cancer

Abstract

Male breast cancer is rare and has been frequently associated with cancer predisposing variants, particularly in BRCA 1 and BRCA 2 genes. ATM pathogenic variants may also increase risk for breast and other cancers. However, less than 10 cases relating ATM mutations and male breast cancer have been previously reported. Therefore, risk estimates and surveillance recommendations are not well established. We report a case of a male patient with breast cancer found to be heterozygous for a pathogenic ATM variant after multigene testing. We also review the literature regarding increased cancer risk associated with ATM germline variants, with emphasis on potential recommendations for surveillance and follow-up.

Biomarkers in Breast Cancer: An Old Story with a New End

“…Among the most common BC susceptibility genes is the ataxia-telangiectasia mutated (ATM), a gene with pathogenic or probably pathogenic variants of moderate penetrance associated with the DNA double-strand break repair mechanism and which has a mutation frequency of 0.78% in patients with BC [74]. ATM gene expresses proteins that participate in DNA repair and cell cycle regulation, which is critical in situations of cell stress and DNA damage response [74,79,80].…”

“…ATM gene mutations have moderate penetrance, and heterozygous carriers have a 2-5 relative risk of developing BC, mostly hormone-receptor-or HER2-positive [79,80]. Many BC patients with ATM mutations develop an intermediate and high-grade disease, with higher chance of lymph node metastasis, more aggressive tumors, and worse prognosis [81].…”

“…Toss et al[74], Cunha et al[79], and Moslemi et al[80] PALB2 Tumor suppressor gene that encodes PALB2, responsible for BRCA2 nuclear localization and DNA damage repair. Nepomuceno et al[84] ER: estrogen receptor; PR: progesterone receptor.…”

Genetic Landscape of Male Breast Cancer

“…In a large association study including only women, the presence of a protein-truncating variant in ATM was linked to an increased risk of BC ( p < 0.0001), with an OR of 2.10 [ 117 ]. Data on ATM PVs and MBC is very scarce [ 118 ]. Recently, a study including patients referred for genetic testing due to personal and/or family histories of cancer found the risk of BC in men harboring an ATM PV to be 1.72 higher (95% CI, 1.08–2.75) [ 119 ].…”