[Adjuvant irradiation in breast cancer patients with ATM gene heterozygous mutations: special focus on clinical efficacy/toxicity].
Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to defective cell cycle control and genomic instability due to the impaired repair of DNA double strand breaks. Although increased radiosensitivity in ATM heterozygous patients has been suggested in preclinical data, clinical implication of ATM variant remains debated. Despite frequent in vitro hypersensitivity in patients with severe radiation-induced delayed toxicity, heterozygoty for ATM gene does not represent the major cause of unexpected complications after radiation therapy. This might be partially due to potential coexistence of alterations in additional genes that would play a role in development of late radiation-induced adverse response. Although several data suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis at lower doses compared with patients who did not possess these genetic alterations, the relationship between the presence of ATM mutations or sequence variants and radiation-induced toxicity remains controversial in part because of their biological and functional significance. Considering the lack of prospective data, patients with ATM mutation should be considered as candidates for both dose volume and dose reduction clinical trials.
Chargari
C
C
Département de radiothérapie, institut Curie, 75005 Paris, France.
Kirova
Y M
YM
Even
C
C
Monnier
L
L
Dendale
R
R
Campana
F
F
Fourquet
A
A
D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D018714:Radiotherapy, Adjuvant; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases