title: The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2.
abstract: Breast cancers arising in carriers of mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, differ histologically from each other and from breast cancers unselected for a family history. However, a substantial proportion of families with multiple cases of breast cancer is not attributable to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancers in non-BRCA1/2 families were of lower grade (P = 0.0018), showed fewer mitoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocytic infiltrate (P < 0.0001), a lesser extent of the tumor with a continuous pushing margin (P = 0.004), a lesser extent of the tumor composed of solid sheets of cells (P = 0.0047), less necrosis (P = 0.002), and wereparison with BRCA2 tumors, non-BRCA1/2 tumors were lower grade (P = 0.017) and exhibited less pleomorphism (P = 0.01) and more tubule formation (P = 0.05). In comparison with control breast cancers unselected for a family history of the disease, non-BRCA1/2 tumors were of significantly lower grade (P = 0.001), showed less pleomorphism (P = 0.0002), and had a lower mitotic count (P = 0.003). The results indicate that non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BRCA2 breast cancers and are overall of lower grade. They also suggest that non-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.
authors.affiliation: Department of Histopathology, University College London Medical School, United Kingdom.
authors.forename: S R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.forename: J
authors.initials: J
authors.lastname: Jacquemier
authors.forename: J P
authors.initials: JP
authors.lastname: Sloane
authors.forename: T J
authors.initials: TJ
authors.lastname: Anderson
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: D
authors.initials: D
authors.lastname: Venter
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.forename: A
authors.initials: A
authors.lastname: Antoniou
authors.forename: L
authors.initials: L
authors.lastname: McGuffog
authors.forename: E
authors.initials: E
authors.lastname: Smyth
authors.forename: C M
authors.initials: CM
authors.lastname: Steel
authors.forename: N
authors.initials: N
authors.lastname: Haites
authors.forename: R J
authors.initials: RJ
authors.lastname: Scott
authors.forename: D
authors.initials: D
authors.lastname: Goldgar
authors.forename: S
authors.initials: S
authors.lastname: Neuhausen
authors.forename: P A
authors.initials: PA
authors.lastname: Daly
authors.forename: W
authors.initials: W
authors.lastname: Ormiston
authors.forename: R
authors.initials: R
authors.lastname: McManus
authors.forename: S
authors.initials: S
authors.lastname: Scherneck
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: P A
authors.initials: PA
authors.lastname: Futreal
authors.forename: J
authors.initials: J
authors.lastname: Peto
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bignon
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D008940:Mitotic Index; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors