Ataxia–telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review

Current oncology

K.J. Jerzak¹ 

[1]University of Toronto

关键词: ATM;    Gene panel assay;    breastGenetic testing;    ataxia–telangiectasia;    breast cancer;    gene panel assays cancer;    screening;   

DOI  :  10.3747/co.25.3707

学科分类：肿瘤学

来源: Multimed, Inc.

【 摘 要 】

BackgroundDespite the fact that heterozygosity for a pathogenicATMvariant is present in 1%–2% of the adult population, clinical guidelines to inform physicians and genetic counsellors about optimal management in that population are lacking. MethodsIn this narrative review, we describe the challenges and controversies in the management of women who are heterozygous for a pathogenicATMvariant with respect to screening for breast and other malignancies, to choices for systemic therapy, and to decisions about radiation therapy. ResultsGiven that the lifetime risk for breast cancer in women who are heterozygous for a pathogenicATMvariant is likely greater than 25%, those women should undergo annual mammographic screening starting at least by 40 years of age. For women in this group who have a strong family history of breast cancer, earlier screening with both magnetic resonance imaging and mammography should be considered. High-quality data to inform the management of established breast cancer in carriers of pathogenicATMvariants are lacking. Although deficiency in theATMgene product might confer sensitivity to dna-damaging pharmaceuticals such as inhibitors of poly (adp–ribose) polymerase or platinum agents, prospective clinical trials have not been conducted in the relevant patient population. Furthermore, the evidence with respect to radiation therapy is mixed; some data suggest increased toxicity, and other data suggest improved clinical benefit from radiation in women who are carriers of a pathogenicATMvariant. ConclusionsAs in the 2017 U.S. National Comprehensive Cancer Network guidelines, we recommend high-risk imaging for women in Ontario who are heterozygous for a pathogenicATMvariant. Currently,ATMcarrier status should not influence decisions about systemic or radiation therapy in the setting of an established breast cancer diagnosis.

【 授权许可】

Unknown