open access

Vol 24, No 6 (2019)
Published online: 2019-11-01
Submitted: 2019-05-24
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Increased radiation toxicity with germline ATM variant of uncertain clinical significance

Brandon T. Mullins, Gaorav Gupta
DOI: 10.1016/j.rpor.2019.09.008
·
Rep Pract Oncol Radiother 2019;24(6):672-680.

open access

Vol 24, No 6 (2019)
Published online: 2019-11-01
Submitted: 2019-05-24

Abstract

Background

While patients with ataxia telangiectasia are known to have increased radiation sensitivity, patients with germline heterozygous ataxia telangiectasia mutated (ATM) mutations can have widely varying functional and clinical effects, which can make management decisions difficult. With an increased prevalence of gene panel-based testing for breast cancer patients, radiation oncologists are increasingly confronted with patients who carry germline ATM variants of uncertain clinical significance. This study describes the clinical courses and outcomes of 5 breast cancer patients with varying germline heterozygous ATM mutations undergoing radiation therapy at our institution in order to provide additional knowledge of the varying clinical effects to aid future decision making.

Case Series

We identified 5 patients with breast cancer and varying germline heterozygous ATM mutations treated at the University of North Carolina Hospitals between 2015 and 2017. The median age at breast cancer diagnosis for the patient series was 46. Clinical effects of radiation treatment varied amongst the 5 patients. The one patient with a pathogenic ATM mutation had no increased radiation related toxicity. Of the 4 patients with ATM variants of uncertain significance, one patient had increased radiation sensitivity with Grade 3 dermatitis. All patients have remained recurrence free with a median duration of 18 months.

Conclusion

Our data illustrates that patients with germline heterozygous ATM mutations can have widely varying clinical effects with radiation therapy. Given the possibility of unpredictable deleterious effects, our study highlights the importance of caution and careful consideration when devising the multi-modality management strategy in these patients.

Abstract

Background

While patients with ataxia telangiectasia are known to have increased radiation sensitivity, patients with germline heterozygous ataxia telangiectasia mutated (ATM) mutations can have widely varying functional and clinical effects, which can make management decisions difficult. With an increased prevalence of gene panel-based testing for breast cancer patients, radiation oncologists are increasingly confronted with patients who carry germline ATM variants of uncertain clinical significance. This study describes the clinical courses and outcomes of 5 breast cancer patients with varying germline heterozygous ATM mutations undergoing radiation therapy at our institution in order to provide additional knowledge of the varying clinical effects to aid future decision making.

Case Series

We identified 5 patients with breast cancer and varying germline heterozygous ATM mutations treated at the University of North Carolina Hospitals between 2015 and 2017. The median age at breast cancer diagnosis for the patient series was 46. Clinical effects of radiation treatment varied amongst the 5 patients. The one patient with a pathogenic ATM mutation had no increased radiation related toxicity. Of the 4 patients with ATM variants of uncertain significance, one patient had increased radiation sensitivity with Grade 3 dermatitis. All patients have remained recurrence free with a median duration of 18 months.

Conclusion

Our data illustrates that patients with germline heterozygous ATM mutations can have widely varying clinical effects with radiation therapy. Given the possibility of unpredictable deleterious effects, our study highlights the importance of caution and careful consideration when devising the multi-modality management strategy in these patients.

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Keywords

ATM; VUS; IDC; DCIS; IMN; ALND; SLNB; ddAC; TC; TCH; ER; PR; Her2; ATM; Ataxia telangiectasia; Breast cancer; Radiation therapy; Toxicity; VUS

About this article
Title

Increased radiation toxicity with germline ATM variant of uncertain clinical significance

Journal

Reports of Practical Oncology and Radiotherapy

Issue

Vol 24, No 6 (2019)

Pages

672-680

Published online

2019-11-01

DOI

10.1016/j.rpor.2019.09.008

Bibliographic record

Rep Pract Oncol Radiother 2019;24(6):672-680.

Keywords

ATM
VUS
IDC
DCIS
IMN
ALND
SLNB
ddAC
TC
TCH
ER
PR
Her2
ATM
Ataxia telangiectasia
Breast cancer
Radiation therapy
Toxicity
VUS

Authors

Brandon T. Mullins
Gaorav Gupta

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