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Clinical Investigations

BRCA-associated Breast Cancer: Absence of a Characteristic Immunophenotype

Marc Robson, Prabha Rajan, Paul Peter Rosen, Theresa Gilewski, Yashar Hirschaut, Peter Pressman, Bruce Haas, Larry Norton and Kenneth Offit
Marc Robson
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Prabha Rajan
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Paul Peter Rosen
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Theresa Gilewski
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Yashar Hirschaut
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Peter Pressman
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Bruce Haas
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Larry Norton
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Kenneth Offit
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DOI:  Published May 1998
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Abstract

To characterize the biological features of breast cancer associated with germ-line mutations in BRCA1 and BRCA2, invasive tumors were studied from 58 Jewish women ascertained through studies of early-onset breast cancer. All women were tested for the BRCA1 founder mutations 187delAG (commonly known as 185delAG) and 5385insC (commonly known as 5382insC) and the BRCA2 founder mutation 6174delT. Mutations were detected in 17 of 58 (29.3%) women. Comparing BRCA-associated breast cancers (BABCs) to cases arising in women without founder mutations, no differences were noted in tumor size, tumor stage, or frequency of axillary nodal involvement. Infiltrating ductal carcinoma was the predominant histological type in both groups. BABCs were significantly more likely to be of histological grade III (100 versus 63%; P = 0.04), estrogen receptor negative (75 versus 35%; P = 0.004), and HER2/neu negative (87 versus 58%; P = 0.04). An associated intraductal component was present in 59% of BABCs and 76% of cancers not associated with mutations (P = not significant). A high Ki-67 labeling index was more commonly observed in BABCs than in cases without mutations (83 versus 48%; P = 0.09). There were no differences between the two groups in the frequency of expression of epidermal growth factor receptor, cathepsin D, bcl-2, p27, p53, or cyclin D. There were no significant differences in relapse-free or overall survival.

These observations suggest that breast cancers arising in Jewish women with germ-line BRCA founder mutations have a greater proliferative potential than cancers in women without such mutations. Additional studies of BABC are required to determine the nature and implications of additional genetic abnormalities occurring in these tumors.

Footnotes

  • ↵1 Supported in part by Specialized Program of Research Excellence Grant P50 CA94027 from the National Cancer Institute. M. R. is supported by American Cancer Society Physician's Research Training Award PRTA-38.

  • ↵2 To whom requests for reprints should be addressed, at Clinical Genetics Service, Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. E-mail: robsonm@mskcc.org.

  • Received October 21, 1997.
  • Accepted February 27, 1998.
  • ©1998 American Association for Cancer Research.
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May 1998
Volume 58, Issue 9
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BRCA-associated Breast Cancer: Absence of a Characteristic Immunophenotype
Marc Robson, Prabha Rajan, Paul Peter Rosen, Theresa Gilewski, Yashar Hirschaut, Peter Pressman, Bruce Haas, Larry Norton and Kenneth Offit
Cancer Res May 1 1998 (58) (9) 1839-1842;

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BRCA-associated Breast Cancer: Absence of a Characteristic Immunophenotype
Marc Robson, Prabha Rajan, Paul Peter Rosen, Theresa Gilewski, Yashar Hirschaut, Peter Pressman, Bruce Haas, Larry Norton and Kenneth Offit
Cancer Res May 1 1998 (58) (9) 1839-1842;
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