Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations: no observation of increased radiation-induced acute, or late effects

Background and purpose: Reports on increased late subcutaneous toxicity after radiation therapy (RT) in breast cancer patients carrying ATM gene mutations has raised concerns about RT as part of the management in these patients. The impact of ataxia-telangiectasia (A-T) heterozygosity on clinical radiosensitivity remains a matter of debate while clinical data are scarce. Patients and methods: Between September 1995 and December 2002 genomic DNA samples were collected from 1100 unselected breast cancer patients receiving adjuvant radiotherapy at our department. Using mutation-specific assays, we screened for frequent ATM gene mutations. Analysis of acute and late radiation-related toxicity for skin and subcutaneous normal tissue was performed in patients identified as A-T heterozygotes applying common toxicity criteria (CTC) and LENT/SOMA (late effects on normal tissue/subjective objective management analytic) scoring criteria, respectively. Results: Eleven patients were identified to be heterozygous for a pathogenic ATM gene mutation. Ten patients had received at least one course of RT. Median follow-up after completion of radiotherapy was 5.1 years (range 1.7-7.2). There was no evidence of increased radiation-induced acute or late skin or subcutaneous reactions in patients treated with linac-based RT. One patient failed distantly and was subsequently irradiated at four different sites for bone and brain metastases. Local relapse occurred in the single patient who had declined adjuvant RT following breast conservative therapy. Conclusions: Our results do not provide evidence for a relative contraindication to adjuvant RT in A-T heterozygous breast cancer patients. Due to their increased cellular radiosensitivity, these patients may differentially benefit from RT and qualify for dose and volume reduction trials. (C) 2003 Elsevier Ireland Ltd. All rights reserved.