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

Abstract

<h3>Purpose/Objective(s)</h3> There is mixed and limited scientific evidence regarding radiotherapy (RT) tolerance in carriers of a pathogenic, germline <b>ATM</b> variant. The ASTRO-ASCO-SSO guidelines on management of hereditary breast cancer suggest offering RT to these patients if clinically indicated. We investigate RT toxicity for carriers of either a pathogenic <b>ATM</b> variant, or variant of unknown significance (VUS), in <b>ATM</b>. <h3>Materials/Methods</h3> Patients with a breast cancer history who had hereditary genetic testing and were found to carry either a pathogenic variant or VUS in <b>ATM</b> were identified. For those who received RT at our institution, toxicity metrics were recorded including dermatitis (scored per CTCAE version 4.0), moist desquamation, and cosmetic outcome (scored per Harvard scale). Fisher's exact test for count data was performed to compare toxicity between the two cohorts. Wilcoxon rank-sum testing was performed to assess for differences in cohort patient characteristics. <h3>Results</h3> Forty-four carriers of a pathogenic <b>ATM</b> variant, and 163 carriers of an <b>ATM</b> VUS, were identified. Fifteen pathogenic and 56 VUS patients, respectively, received RT at our institution and had available toxicity records. The cohorts did not statistically differ in race, medical comorbidities, clinical or pathologic T-stage, hormone receptor status, receipt of chemotherapy, fractionation schedule, or receipt of a boost. No patients had a known collagen vascular disease. 77% of patients (55/71) had breast conservation. 62% received whole breast RT, 7% received chest wall RT, 4.2% received partial breast RT, and 26.8% received whole breast or chest wall RT with regional nodal RT. 58% received conventionally-fractionated RT, and 38% received hypofractionated RT. Median toxicity follow up was 11.6 months. 29% (4/15) of pathogenic carriers and 26.4% (14/56) of VUS carriers developed moist desquamation (<i>P</i> = 0.7). The rates of grade 2+ acute dermatitis were 71% in pathogenic carriers and 57% in VUS carriers (<i>P</i> = 0.4). 100% of pathogenic carriers and 91% of VUS carriers had a good/excellent cosmetic outcome at first follow up (<i>P</i> > 0.9). No patients with a pathogenic variant had a fair or poor cosmetic outcome at last follow up. <h3>Conclusion</h3> RT is well tolerated in carriers of a pathogenic <b>ATM</b> variant, with rates of grade 2+ dermatitis and moist desquamation comparable to a matched VUS cohort. High rates of good or excellent cosmetic outcome were seen following treatment. Further analyses including an <b>ATM</b> wild type cohort and continued detailed toxicity documentation/analysis is on-going to elucidate longer term morbidity.