title: Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis.
abstract: OBJECTIVE
  Breast tumors of BRCA1 mutation carriers and those of early onset breast cancer cases share similar histological features, being generally high-grade, highly proliferative, aneuploid tumors that are predominantly estrogen- and progesterone-receptor negative. Because histological features of tumors of premenopausal women differ from those of tumors of older women, we sought to determine whether the immunophenotype of breast tumors of BRCA1 mutation carriers was influenced by age at diagnosis.
  
  
  METHODS
  We examined 31 breast tumors from BRCA1 mutation carriers and compared them with 81 tumors of age-matched (plus or minus 5 years) breast cancer patients unselected for family history. Tumors were further matched for histology, grade, and size. Paraffin-embedded tumor tissues were examined for protein expression of estrogen receptor (ER), PR, Ki-67, cyclin D1, TP53, HER2, beta-catenin, and cyclin E using immunohistochemical approaches.
  
  
  RESULTS
  ER (P = 0.01), PR (P = 0.06), and cyclin D1 (P = 0.002) were less frequently expressed and Ki-67 (P = 0.01) and beta-catenin (P = 0.04) were more frequently expressed in tumors of BRCA1 mutation carriers than controls. After age stratification, we found a significant difference in the frequency of tumors of BRCA1 mutation carriers diagnosed before 50 years of age compared with age-matched controls that stained positive for ER (P = 0.01), PR (P = 0.03), Ki-67 (P = 0.008), cyclin D1 (P < 0.001), HER2 (P = 0.04), and beta-catenin (P = 0.05). However, no significant differences were observed in tumors of BRCA1 mutation carriers diagnosed at age 50 or older compared with age-matched controls.
  
  
  CONCLUSIONS
  These data suggest that age at diagnosis, possibly related to menopausal status, may be an important factor in the expression of specific proteins in breast tumors of BRCA1 mutation carriers.
authors.affiliation: Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Vaziri
authors.forename: L M
authors.initials: LM
authors.lastname: Krumroy
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.forename: G T
authors.initials: GT
authors.lastname: Budd
authors.forename: G
authors.initials: G
authors.lastname: Darlington
authors.forename: J
authors.initials: J
authors.lastname: Myles
authors.forename: R R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: G
authors.initials: G
authors.lastname: Casey
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000032:analysis; D019927:Cyclin E / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012042:Registries; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051176:beta Catenin
chemical_list: D019313:BRCA1 Protein; D019938:Cyclin D1; D019927:Cyclin E; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C495270:CTNNB1 protein, human