BRCA1 and BRCA2 hereditary breast carcinoma phenotypes

Joseph N. Marcus, David L. Page, Patrice Watson, Steven A. Narod, Gilbert M. Lenoir, Henry T. Lynch

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Mutations in two major susceptibility genes, BRCA1 and BRCA2, account for most hereditary breast carcinoma (HBC). METHODS. BRCA1 and BRCA2 genotype-phenotype associations are reviewed with special emphasis on pathologic characteristics. Tumor spectra in families, prognosis phenotype, and molecular biologic correlates with phenotype are also explored. RESULTS. BRCA1 is an estrogen-inducable cell cycle-associated protein with anti- proliferation and tumor suppressor function. Less is known about BRCA2 protein but it has some similarities to BRCA1. Release of cells from BRCA1 control through germline mutations gives rise to genetically evolved breast carcinomas with a highly distinctive and correspondent proliferator phenotype featuring aneuploidy, high S-phase fraction, high mitotic grade, and medullary carcinomas. BRCA1 HBCs also show a deficit of ductal carcinoma in situ and invasive lobular, tubular, tubulo-lobular, and cribriform ('tubular- lobular group' [TLG]) carcinomas. In contrast, the BRCA2 HBC phenotype, although less well determined and possibly more heterogeneous, appears to lack the more extensive BRCA1 proliferator characteristics but may have excess TLG carcinomas. Despite their adverse pathoprognostic features, BRCA1 HBCs have paradoxically better disease free survivals than non-BRCA1 HBCs, but data are not yet clear whether this effect can be attributed to BRCA2 HBC generally. Larger studies are needed to assess potential heterogeneity. CONCLUSIONS. Although the phenotypes are presently imperfectly resolved, early studies indicate differences between BRCA1 and BRCA2 HBC.

Original languageEnglish
Pages (from-to)543-556
Number of pages14
JournalCancer
Volume80
Issue number3 SUPPL.
StatePublished - 1997

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Breast Neoplasms
Phenotype
Lobular Carcinoma
BRCA2 Protein
BRCA2 Gene
BRCA1 Gene
Cell Cycle Proteins
Medullary Carcinoma
Carcinoma, Intraductal, Noninfiltrating
Germ-Line Mutation
Genetic Association Studies
Aneuploidy
S Phase
Disease-Free Survival
Neoplasms
Estrogens
Mutation

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Marcus, J. N., Page, D. L., Watson, P., Narod, S. A., Lenoir, G. M., & Lynch, H. T. (1997). BRCA1 and BRCA2 hereditary breast carcinoma phenotypes. Cancer, 80(3 SUPPL.), 543-556.

BRCA1 and BRCA2 hereditary breast carcinoma phenotypes. / Marcus, Joseph N.; Page, David L.; Watson, Patrice; Narod, Steven A.; Lenoir, Gilbert M.; Lynch, Henry T.

In: Cancer, Vol. 80, No. 3 SUPPL., 1997, p. 543-556.

Research output: Contribution to journalArticle

Marcus, JN, Page, DL, Watson, P, Narod, SA, Lenoir, GM & Lynch, HT 1997, 'BRCA1 and BRCA2 hereditary breast carcinoma phenotypes', Cancer, vol. 80, no. 3 SUPPL., pp. 543-556.
Marcus JN, Page DL, Watson P, Narod SA, Lenoir GM, Lynch HT. BRCA1 and BRCA2 hereditary breast carcinoma phenotypes. Cancer. 1997;80(3 SUPPL.):543-556.
Marcus, Joseph N. ; Page, David L. ; Watson, Patrice ; Narod, Steven A. ; Lenoir, Gilbert M. ; Lynch, Henry T. / BRCA1 and BRCA2 hereditary breast carcinoma phenotypes. In: Cancer. 1997 ; Vol. 80, No. 3 SUPPL. pp. 543-556.
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AU - Lynch, Henry T.

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N2 - BACKGROUND. Mutations in two major susceptibility genes, BRCA1 and BRCA2, account for most hereditary breast carcinoma (HBC). METHODS. BRCA1 and BRCA2 genotype-phenotype associations are reviewed with special emphasis on pathologic characteristics. Tumor spectra in families, prognosis phenotype, and molecular biologic correlates with phenotype are also explored. RESULTS. BRCA1 is an estrogen-inducable cell cycle-associated protein with anti- proliferation and tumor suppressor function. Less is known about BRCA2 protein but it has some similarities to BRCA1. Release of cells from BRCA1 control through germline mutations gives rise to genetically evolved breast carcinomas with a highly distinctive and correspondent proliferator phenotype featuring aneuploidy, high S-phase fraction, high mitotic grade, and medullary carcinomas. BRCA1 HBCs also show a deficit of ductal carcinoma in situ and invasive lobular, tubular, tubulo-lobular, and cribriform ('tubular- lobular group' [TLG]) carcinomas. In contrast, the BRCA2 HBC phenotype, although less well determined and possibly more heterogeneous, appears to lack the more extensive BRCA1 proliferator characteristics but may have excess TLG carcinomas. Despite their adverse pathoprognostic features, BRCA1 HBCs have paradoxically better disease free survivals than non-BRCA1 HBCs, but data are not yet clear whether this effect can be attributed to BRCA2 HBC generally. Larger studies are needed to assess potential heterogeneity. CONCLUSIONS. Although the phenotypes are presently imperfectly resolved, early studies indicate differences between BRCA1 and BRCA2 HBC.

AB - BACKGROUND. Mutations in two major susceptibility genes, BRCA1 and BRCA2, account for most hereditary breast carcinoma (HBC). METHODS. BRCA1 and BRCA2 genotype-phenotype associations are reviewed with special emphasis on pathologic characteristics. Tumor spectra in families, prognosis phenotype, and molecular biologic correlates with phenotype are also explored. RESULTS. BRCA1 is an estrogen-inducable cell cycle-associated protein with anti- proliferation and tumor suppressor function. Less is known about BRCA2 protein but it has some similarities to BRCA1. Release of cells from BRCA1 control through germline mutations gives rise to genetically evolved breast carcinomas with a highly distinctive and correspondent proliferator phenotype featuring aneuploidy, high S-phase fraction, high mitotic grade, and medullary carcinomas. BRCA1 HBCs also show a deficit of ductal carcinoma in situ and invasive lobular, tubular, tubulo-lobular, and cribriform ('tubular- lobular group' [TLG]) carcinomas. In contrast, the BRCA2 HBC phenotype, although less well determined and possibly more heterogeneous, appears to lack the more extensive BRCA1 proliferator characteristics but may have excess TLG carcinomas. Despite their adverse pathoprognostic features, BRCA1 HBCs have paradoxically better disease free survivals than non-BRCA1 HBCs, but data are not yet clear whether this effect can be attributed to BRCA2 HBC generally. Larger studies are needed to assess potential heterogeneity. CONCLUSIONS. Although the phenotypes are presently imperfectly resolved, early studies indicate differences between BRCA1 and BRCA2 HBC.

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