title: Pathologic features and immunophenotype of estrogen receptor-positive breast cancers in BRCA1 mutation carriers.
abstract: Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER-) with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than ER- BRCA1-related cancers to be of pure invasive ductal type (P<0.001) and to be of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P<0.0001), CK14 (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1-related cancers were significantly more often of invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more frequently had a high mitotic rate (P=0.0003), and were more often CK14+ (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER- BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1-related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1-related cancers.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Kaplan
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Laura C
authors.initials: LC
authors.lastname: Collins
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Karen
authors.initials: K
authors.lastname: Krag
authors.forename: Katharina
authors.initials: K
authors.lastname: Fetten
authors.forename: Anne
authors.initials: A
authors.lastname: Lincoln
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Tung
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D005355:Fibrosis; D006579:Heterozygote; D006801:Humans; D016130:Immunophenotyping; D009154:Mutation; D009336:Necrosis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases