title: Histopathological features of breast cancer in carriers of ATM gene variants.
abstract: OBJECTIVE
  Germline variants in the ataxia telangiectasia mutated (ATM) gene have been implicated in increased breast cancer risk. The aim of this study was to determine whether the histopathology of breast cancers occurring in ATM variant carriers is distinctive or resembles the described BRCA1 mutation-associated phenotype.
  
  
  METHODS
  The histopathological features of breast cancers occurring in ATM variant carriers from multiple-case breast cancer families were compared with matched controls. The test group included 21 cases of in situ and/or invasive cancer from carriers of either the IVS10-6T-->G, 2424V-->G or 1420L-->F ATM variants in the absence of BRCA1 or BRCA2 mutations. An additional four invasive cancers from carriers of a pathogenic BRCA1 mutation in the context of a familial ATM variant were also examined.
  
  
  RESULTS
  The histopathology of breast cancers in ATM variant-only carriers was not significantly different from controls and known features of BRCA1 mutation-associated cancer were rarely seen. In contrast, these features were prominent in the small group of cases with a pathogenic BRCA1 mutation.
  
  
  CONCLUSIONS
  Breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features and does not resemble the tumour phenotype commonly observed in BRCA1 mutation carriers.
authors.affiliation: Translational Oncology, Sydney West Area Health Service, Sydney, Australia. rosemary_balleine@wmi.usyd.edu.au
authors.forename: R L
authors.initials: RL
authors.lastname: Balleine
authors.forename: R
authors.initials: R
authors.lastname: Murali
authors.forename: A M
authors.initials: AM
authors.lastname: Bilous
authors.forename: G
authors.initials: G
authors.lastname: Farshid
authors.forename: P
authors.initials: P
authors.lastname: Waring
authors.forename: P
authors.initials: P
authors.lastname: Provan
authors.forename: K
authors.initials: K
authors.lastname: Byth
authors.forename: H
authors.initials: H
authors.lastname: Thorne
authors.forename: J A
authors.initials: JA
authors.lastname: Kirk
mesh_terms: D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases