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Increased radiation toxicity with germline ATM variant of uncertain clinical significance.
Rep Pract Oncol Radiother 2019 Nov-Dec; 24(6):672-680RP

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.

Authors+Show Affiliations

Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, CB #7512, Chapel Hill, NC, USA.Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, CB #7512, Chapel Hill, NC, USA. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Pub Type(s)

Case Reports

Language

eng

PubMed ID

31719806

Citation

Mullins, Brandon T., and Gaorav Gupta. "Increased Radiation Toxicity With Germline ATM Variant of Uncertain Clinical Significance." Reports of Practical Oncology and Radiotherapy : Journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology, vol. 24, no. 6, 2019, pp. 672-680.
Mullins BT, Gupta G. Increased radiation toxicity with germline ATM variant of uncertain clinical significance. Rep Pract Oncol Radiother. 2019;24(6):672-680.
Mullins, B. T., & Gupta, G. (2019). Increased radiation toxicity with germline ATM variant of uncertain clinical significance. Reports of Practical Oncology and Radiotherapy : Journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology, 24(6), pp. 672-680. doi:10.1016/j.rpor.2019.09.008.
Mullins BT, Gupta G. Increased Radiation Toxicity With Germline ATM Variant of Uncertain Clinical Significance. Rep Pract Oncol Radiother. 2019;24(6):672-680. PubMed PMID: 31719806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased radiation toxicity with germline ATM variant of uncertain clinical significance. AU - Mullins,Brandon T, AU - Gupta,Gaorav, Y1 - 2019/11/06/ PY - 2019/05/24/received PY - 2019/07/15/revised PY - 2019/09/21/accepted PY - 2020/11/01/pmc-release PY - 2019/11/14/entrez PY - 2019/11/14/pubmed PY - 2019/11/14/medline KW - ALND, Axillary Lymph Node Dissection KW - ATM KW - ATM, Ataxia Telangiectasia Mutated KW - Ataxia telangiectasia KW - Breast cancer KW - DCIS, Ductal Carcinoma In-situ KW - ER, Estrogen Receptor KW - Her2, Human Epidermal Growth Factor Receptor 2 KW - IDC, Invasive Ductal Carcinoma KW - IMN, Internal Mammary Lymph Node KW - PR, Progesterone Receptor KW - Radiation therapy KW - SLNB, Sentinel Lymph Node Biopsy KW - TC, Taxol & Cyclophosphamide KW - TCH, Taxol, Cyclophosphamide, Herceptin KW - Toxicity KW - VUS KW - VUS, Variant of Uncertain Significance KW - ddAC, Dose Dense Adriamycin & Cyclophosphamide SP - 672 EP - 680 JF - Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology JO - Rep Pract Oncol Radiother VL - 24 IS - 6 N2 - 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. SN - 1507-1367 UR - https://www.unboundmedicine.com/medline/citation/31719806/Increased_radiation_toxicity_with_germline_ATM_variant_of_uncertain_clinical_significance DB - PRIME DP - Unbound Medicine ER -
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