Breast Irradiation is Well Tolerated in Carriers of a Pathogenic ATM Variant.

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Practical radiation oncology


PURPOSE: There are mixed and limited data regarding radiotherapy (RT) tolerance in carriers of a germline pathogenic or likely pathogenic (P/LP) ATM variant. We investigated RT-related toxic effects in carriers of an ATM variant who received treatment for breast cancer.

METHODS AND MATERIALS: We identified 71 patients treated with adjuvant radiotherapy for breast cancer who were carriers of a variant in ATM: 15 were classified as P/LP and 56 classified as variants of unknown significance (VUS). We additionally identified 205 consecutively-treated patients during a similar timeframe who were either confirmed ATM wild-type or had no prior genetic testing. RT plans were reviewed. Acute and chronic toxic effects were evaluated using CTCAE version 4.0 criteria. Fisher's exact tests for count data were performed to compare toxic effects between the cohorts (P/LP vs. VUS vs. control). Wilcoxon rank-sum testing was performed to assess for differences in patient characteristics.

RESULTS: The median toxicity follow-up was 19.4 months; median follow-up for the sub-cohorts was 13.3 months (P/LP), 12.6 months (VUS), and 23.3 months (control), respectively. There were no significant differences in radiation plan heterogeneity, receipt of a boost, and size of breast/chest wall planning target volume. There was greater use of hypofractionated RT in the control cohort (p=0.023). After accounting for patient- and treatment-related factors that may impact toxic effects, we found no significant differences with respect to acute dermatitis, hyperpigmentation, moist desquamation, breast/chest wall pain, or breast edema. Additionally, we found no significant differences with respect to chronic breast/chest wall pain, induration, telangiectasia, or cosmetic outcome.

CONCLUSIONS: Radiation therapy as part of the management of breast cancer was well tolerated in carriers of a P/LP ATM variant, with toxic effect profiles that are similar to those seen in patients without known ATM mutations. High rates of excellent or good cosmesis were observed in carriers of a P/LP ATM variant who underwent breast conservation.





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