Breast radiotherapy among ATM-mutation carriers.

Abstract

1504 Background: Syndromes of DNA repair deficiency may confer both cancer predisposition and increased sensitivity to DNA damaging agents, such as ionizing radiation. Whereas homozygous deficiency of ATM causes the ataxia telangiectasia syndrome, heterozygous ATM mutation carriers exhibit increased rates of breast, pancreas and prostate cancers. ATM repairs DNA double-strand breaks; consequently, mutation carriers may exhibit excessive radiotherapeutic (RT) toxicity. We evaluated the tolerability of adjuvant breast radiation in ATM mutation carriers. Methods: We identified 167 ATM mutation carriers presenting to our institution with breast cancer; of these, 91 received RT and records were reviewed for RT-related morbidity. Toxicities were graded per CTCAE v5. Associations of clinicopathologic features with toxicity were evaluated by multivariate regression. Results: Of 91 ATM mutation carriers receiving breast RT, 31% (n = 28) harbored a pathogenic mutation whereas 69% (n = 63) harbored variants of uncertain significance (VUS). 71% (n = 65) underwent lumpectomy and adjuvant whole-breast RT; 29% (n = 26) had mastectomy and PMRT. Nine patients underwent bilateral RT for a total of 100 RT courses. 86% of RT courses comprised whole-breast/chest-wall tangents; 14% were VMAT or protons. Median tangent dose was 50Gy; 62% included an additional boost (median 10Gy) and 48% used a bolus (median thickness 0.3cm). Lymph nodes were treated in 43% (n = 39). At last on-treatment visit, 31% had grade 2 dermatitis, 4% had other grade 2 events (fatigue, seroma, decreased range of motion, or pain), and 1% had grade 3 dermatitis. At 1 year, 13% had grade ≥2 toxicity: grade 2a lymphedema (n = 3), and grade 2 (n = 1) or 3 (n = 2) capsular contracture. At last follow-up, 4 PMRT patients had capsular contracture (3 with grade 2, 1 with grade 3); 1 patient had grade 2b lymphedema. Overall, no patients had significant (grade ≥2) telangiectasias, fibrosis, or fat necrosis; no grade 4 or 5 toxicities were seen. Neither pathogenic ATM mutations nor VUS were associated with acute or late RT toxicities. Conclusions: We found no evidence of excess breast radiation toxicity among ATM mutation carriers, either pathogenic or VUS. Breast conserving therapy can be safely considered in this population.