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Improved survival in women with BRCA-associated ovarian carcinoma†

  1. Ilana Cass M.D.1,‡,*,
  2. Rae Lynn Baldwin Ph.D.1,
  3. Taz Varkey M.D.1,
  4. Roxana Moslehi Ph.D.2,
  5. Steven A. Narod M.D.2,
  6. Beth Y. Karlan M.D.1

Article first published online: 17 APR 2003

DOI: 10.1002/cncr.11310

Issue

Cancer

Cancer

Volume 97, Issue 9, pages 2187–2195, 1 May 2003

Additional Information

How to Cite

Cass, I., Baldwin, R. L., Varkey, T., Moslehi, R., Narod, S. A. and Karlan, B. Y. (2003), Improved survival in women with BRCA-associated ovarian carcinoma. Cancer, 97: 2187–2195. doi: 10.1002/cncr.11310

Author Information

  1. 1

    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center and University of California-Los Angeles School of Medicine, Los Angeles, California

  2. 2

    Center for Research in Women's Health, Sunnybrook Women's College Health Science Center, University of Toronto, Canada

  1. ‡

    Fax: (310) 423-0155

*Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048

  1. †

    See related editorial on pages 2127–9, this issue.

Publication History

  1. Issue published online: 17 APR 2003
  2. Article first published online: 17 APR 2003
  3. Manuscript Accepted: 18 DEC 2002
  4. Manuscript Revised: 9 DEC 2002
  5. Manuscript Received: 11 NOV 2002

Funded by

  • Gynecologic Cancer Foundation/Susan G. Komen Breast Cancer Foundation
  • American Cancer Society, California Division Inc.. Grant Number: 5-3-00
  • Cedars-Sinai Research for Womens Cancers

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Keywords:

  • hereditary ovarian carcinoma;
  • chemosensitivity;
  • BRCA1;
  • BRCA2;
  • p53

Jewish patients with BRCA-associated ovarian carcinoma had improved survival compared with Jewish patients who had sporadic ovarian carcinoma. This improvement in survival was the result of an enhanced response to platinum-based chemotherapy.

See also pages 2127–9.

Abstract

BACKGROUND

The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma.

METHODS

Seventy-one Jewish women with epithelial ovarian carcinoma (EOC) were tested for the three BRCA founder mutations using single-strand conformation polymorphism analysis, heteroduplex analysis, and protein truncation testing. Clinical and histopathologic data were reviewed retrospectively. In vitro chemoresistance was analyzed in 32 patients. Mutations of p53 were studied using immunohistochemical detection of p53 overexpression.

RESULTS

Thirty-four of 71 Jewish patients with EOC (48%) had germline BRCA mutations (BRCA heterozygotes), including 22 BRCA1 mutations and 12 BRCA2 mutations. BRCA heterozygotes were younger compared with Jewish patients who had EOC without mutations (sporadic carcinoma; 50 years vs. 59 years, respectively; P = 0.01). BRCA1 heterozygotes were younger compared with BRCA2 heterozygotes (48 years vs. 57 years, respectively; P = 0.01). Histopathologic tumor features were similar; however, tumors with low malignant potential were seen only in women with sporadic carcinoma. Both groups had equivalent rates of surgical cytoreduction and similar median follow-up (72 months). BRCA heterozygotes had higher response rates to primary therapy compared with patients who had sporadic disease (P = 0.01). In vitro chemoresistance predicted tumor response to platinum chemotherapy correctly in BRCA heterozygotes (P = 0.0096). BRCA heterozygotes with advance-stage disease had improved survival compared with patients who had advanced stage sporadic carcinoma (91 months vs. 54 months, respectively; P = 0.046) and had a longer disease free interval (49 months vs. 19 months, respectively; P = 0.16). p53 overexpression was common in BRCA heterozygotes (80%).

CONCLUSIONS

BRCA1 heterozygotes developed EOC at a younger age compared with BRCA2 heterozygotes and women who had sporadic ovarian carcinoma. BRCA heterozygotes had a better response to platinum chemotherapy compared with women who had sporadic disease, which may have contributed to their improved prognosis. Cancer 2003;97:2187–95. © 2003 American Cancer Society.

DOI 10.1002/cncr.11310

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