Clinical and Pathological Features of Ovarian Cancer in Women with Germ-Line Mutations of BRCA1
Stephen C. Rubin, M.D., Ivor Benjamin, M.D., Kian Behbakht, M.D., Hiroyuki Takahashi, M.D., Ph.D., Mark A. Morgan, M.D., Virginia A. LiVolsi, M.D., Andrew Berchuck, M.D., Michael G. Muto, M.D., Judy E. Garber, M.D., Barbara L. Weber, M.D., Henry T. Lynch, M.D., and Jeff Boyd, Ph.D.
Background We tested the hypothesis that ovarian cancers associatedwith germ-line mutations of BRCA1 have distinct clinical andpathological features as compared with sporadic ovarian cancers.
Methods We reviewed clinical and pathological data on patientswith primary epithelial ovarian cancer found to have germ-linemutations of BRCA1. Survival among patients with advanced-stagecancer and such mutations was compared with that in controlpatients matched for age and stage, grade, and histologic subtypeof the tumors. A combination of single-strand conformation andsequencing analyses was used to examine the 22 coding exonsand intronic splice-donor and splice-acceptor regions of BRCA1for mutations in pathological specimens. Alternatively, somepatients were known to be obligate carriers of the mutant BRCA1gene because of their parental relationships with documentedmutant-gene carriers.
Results We identified 53 patients with germ-line mutations ofBRCA1. The average age at diagnosis was 48 years (range, 28to 78). Histologic examination in 43 of the 53 patients showedserous adenocarcinoma. Thirty-seven tumors were of grade 3,11 were of grade 2, 2 were of grade 1, and 3 were of low malignantpotential. In 38 patients, the tumors were of stage III; 9 patients(including those with tumors of low malignant potential) hadstage I disease, 5 had stage IV, and 1 had stage II. As of June1996, with a median follow-up among survivors of 71 months fromdiagnosis, 20 patients had died of ovarian cancer, 27 had noevidence of the disease, 4 were alive with the disease, and2 had died of other diseases. Actuarial median survival forthe 43 patients with advanced-stage disease was 77 months, ascompared with 29 months for the matched controls (P<0.001).
Conclusions As compared with sporadic ovarian cancers, cancersassociated with BRCA1 mutations appear to have a significantlymore favorable clinical course.
Source Information
From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology (S.C.R., I.B., K.B., H.T., M.A.M., J.B.), the Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine (V.A.L.), and the Division of Hematology and Oncology, Department of Medicine (B.L.W.), University of Pennsylvania Medical Center, Philadelphia; the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, N.C. (A.B.); the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston (M.G.M.); the Division of Cancer Epidemiology and Control, Dana–Farber Cancer Institute, Boston (J.E.G.); and the Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebr. (H.T.L.).
Address reprint requests to Dr. Rubin at the Division of Gynecologic Oncology, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104.
BRCA1 Mutations and Survival in Women with Ovarian Cancer
Cannistra S. A., Whitmore S. E., Burk R. D., Modan B., Johannsson O., Ranstam J., Borg A., Olsson H., Brunet J.-S., Narod S. A., Tonin P., Foulkes W. D., Rubin S. C.
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N Engl J Med 1997;
336:1254-1257, Apr 24, 1997.
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10: 2473-2481
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96: 488-489
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(2003). BRCA1/2 Mutation Status Influences Somatic Genetic Progression in Inherited and Sporadic Epithelial Ovarian Cancer Cases. Cancer Res.
63: 417-423
[Abstract][Full Text]
Pichert, G., Bolliger, B., Buser, K., Pagani, O.
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[Abstract][Full Text]
Rathi, A., Virmani, A. K., Schorge, J. O., Elias, K. J., Maruyama, R., Minna, J. D., Mok, S. C., Girard, L., Fishman, D. A., Gazdar, A. F.
(2002). Methylation Profiles of Sporadic Ovarian Tumors and nonmalignant Ovaries from High-Risk Women. Clin. Cancer Res.
8: 3324-3331
[Abstract][Full Text]
Cooper, B. C., Sood, A. K., Davis, C. S., Ritchie, J. M., Sorosky, J. I., Anderson, B., Buller, R. E.
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[Abstract][Full Text]
Rao, G. G., Ashfaq, R., Schorge, J. O.
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99: 944-946
[Abstract][Full Text]
Buller, R. E., Shahin, M. S., Geisler, J. P., Zogg, M., De Young, B. R., Davis, C. S.
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van Roosmalen, M. S., Verhoef, L. C.G., Stalmeier, P. F.M., Hoogerbrugge, N., van Daal, W. A.J.
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Ben David, Y., Chetrit, A., Hirsh-Yechezkel, G., Friedman, E., Beck, B.D., Beller, U., Ben-Baruch, G., Fishman, A., Levavi, H., Lubin, F., Menczer, J., Piura, B., Struewing, J.P., Modan, B.
(2002). Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors. JCO
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[Abstract][Full Text]
Sekine, M., Nagata, H., Tsuji, S., Hirai, Y., Fujimoto, S., Hatae, M., Kobayashi, I., Fujii, T., Nagata, I., Ushijima, K., Obata, K., Suzuki, M., Yoshinaga, M., Umesaki, N., Satoh, S., Enomoto, T., Motoyama, S., Tanaka, K.
(2001). Mutational Analysis of BRCA1 and BRCA2 and Clinicopathologic Analysis of Ovarian Cancer in 82 Ovarian Cancer Families: Two Common Founder Mutations of BRCA1 in Japanese Population. Clin. Cancer Res.
7: 3144-3150
[Abstract][Full Text]
Peshkin, B. N., DeMarco, T. A., Brogan, B. M., Lerman, C., Isaacs, C.
(2001). BRCA1/2 Testing: Complex Themes in Result Interpretation. JCO
19: 2555-2565
[Abstract][Full Text]
Buller, R. E., Lallas, T. A., Shahin, M. S., Sood, A. K., Hatterman-Zogg, M., Anderson, B., Sorosky, J. I., Kirby, P. A.
(2001). The p53 Mutational Spectrum Associated with BRCA1 Mutant Ovarian Cancer. Clin. Cancer Res.
7: 831-838
[Abstract][Full Text]
McGuire, V., Whittemore, A. S., Norris, R., Oakley-Girvan, I.
(2000). Survival in Epithelial Ovarian Cancer Patients with Prior Breast Cancer. Am J Epidemiol
152: 528-532
[Abstract][Full Text]
Eisen, A., Rebbeck, T. R., Wood, W. C., Weber, B. L.
(2000). Prophylactic Surgery in Women With a Hereditary Predisposition to Breast and Ovarian Cancer. JCO
18: 1980-1995
[Abstract][Full Text]
Boyd, J., Sonoda, Y., Federici, M. G., Bogomolniy, F., Rhei, E., Maresco, D. L., Saigo, P. E., Almadrones, L. A., Barakat, R. R., Brown, C. L., Chi, D. S., Curtin, J. P., Poynor, E. A., Hoskins, W. J.
(2000). Clinicopathologic Features of BRCA-Linked and Sporadic Ovarian Cancer. JAMA
283: 2260-2265
[Abstract][Full Text]
Matias-Guiu, X., Bussaglia, E., Catasus, L., Lagarda, H., Gras, E., Machin, P., Prat, J., Lin, W. M., Muller, C. Y.
(2000). Correspondence re: W. M. Lin et al., Loss of Heterozygosity and Mutational Analysis of the PTEN/MMAC1 Gene in Synchronous Endometrial and Ovarian Carcinomas. Clin. Cancer Res., 4: 2577-2583, 1998.. Clin. Cancer Res.
6: 1598-1600
[Full Text]
Schrag, D., Kuntz, K. M., Garber, J. E., Weeks, J. C.
(2000). Life Expectancy Gains From Cancer Prevention Strategies for Women With Breast Cancer and BRCA1 or BRCA2 Mutations. JAMA
283: 617-624
[Abstract][Full Text]
Offit, K.
(2000). Genetic Prognostic Markers for Colorectal Cancer. NEJM
342: 124-125
[Full Text]
Li, Q., Kopecky, K. J., Mohan, A., Willman, C. L., Appelbaum, F. R., Weick, J. K., Issa, J.-P. J.
(1999). Estrogen Receptor Methylation Is Associated with Improved Survival in Adult Acute Myeloid Leukemia. Clin. Cancer Res.
5: 1077-1084
[Abstract][Full Text]
Kasprzak, L., Foulkes, W. D, Shelling, A. N
(1999). Fortnightly review: Hereditary ovarian carcinoma. BMJ
318: 786-789
[Full Text]
Lee, J. S., Wacholder, S., Struewing, J. P., McAdams, M., Pee, D., Brody, L. C., Tucker, M. A., Hartge, P.
(1999). Survival After Breast Cancer in Ashkenazi Jewish BRCA1 and BRCA2 Mutation Carriers. JNCI J Natl Cancer Inst
91: 259-263
[Abstract][Full Text]
Pharoah, P. D. P., Easton, D. F., Stockton, D. L., Gayther, S., Ponder, B. A. J.
(1999). Survival in Familial, BRCA1-associated, and BRCA2-associated EpithelialOvarian Cancer. Cancer Res.
59: 868-871
[Abstract][Full Text]
LU, K. H., CRAMER, D. W., MUTO, M. G., LI, E. Y., NILOFF, J., MOK, S. C.
(1999). A Population-Based Study of BRCA1 and BRCA2 Mutations in Jewish Women With Epithelial Ovarian Cancer. Obstet Gynecol
93: 34-37
[Abstract][Full Text]
Frank, T. S.
(1998). Hereditary Risk of Breast and Ovarian Carcinoma: The Role of the Oncologist. The Oncologist
3: 403-412
[Abstract][Full Text]
Tengs, T. O., Winer, E. P., Paddock, S., Aguilar-Chavez, O., Berry, D. A.
(1998). Testing for the BRCA1 and BRCA2 Breast-Ovarian Cancer Susceptibility Genes: A Decision Analysis. Med Decis Making
18: 365-375
[Abstract]
Lynch, H. T., Casey, M. J., Shaw, T. G., Lynch, J. F.
(1998). Hereditary Factors in Gynecologic Cancer. The Oncologist
3: 319-338
[Abstract][Full Text]
Rubin, S. C.
(1998). Chemoprevention of Hereditary Ovarian Cancer. NEJM
339: 469-471
[Full Text]
Kodish, E., Wiesner, G. L., Mehlman, M., Murray, T.
(1998). Genetic Testing for Cancer Risk: How to Reconcile the Conflicts. JAMA
279: 179-181
[Full Text]
Grogan, L., Kirsch, I.R.
(1997). Genetic Testing for Cancer Risk Assessment: A Review. The Oncologist
2: 208-222
[Abstract][Full Text]
Schrag, D., Kuntz, K. M., Garber, J. E., Weeks, J. C.
(1997). Decision Analysis -- Effects of Prophylactic Mastectomy and Oophorectomy on Life Expectancy among Women with BRCA1 or BRCA2 Mutations. NEJM
336: 1465-1471
[Abstract][Full Text]
Cannistra, S. A., Whitmore, S. E., Burk, R. D., Modan, B., Johannsson, O., Ranstam, J., Borg, A., Olsson, H., Brunet, J.-S., Narod, S. A., Tonin, P., Foulkes, W. D., Rubin, S. C.
(1997). BRCA1 Mutations and Survival in Women with Ovarian Cancer. NEJM
336: 1254-1257
[Full Text]
Stratton, J. F., Gayther, S. A., Russell, P., Dearden, J., Gore, M., Blake, P., Easton, D., Ponder, B. A.J.
(1997). Contribution of BRCA1 Mutations to Ovarian Cancer. NEJM
336: 1125-1130
[Abstract][Full Text]
Olopade, O. I.
(1996). Genetics in Clinical Cancer Care -- The Future is Now. NEJM
335: 1455-1456
[Full Text]
