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.
Extract |
Full Text
N Engl J Med 1997;
336:1254-1257, Apr 24, 1997.
Correspondence
This article has been cited by other articles:
Stensheim, H., Moller, B., van Dijk, T., Fossa, S. D.
(2009). Cause-Specific Survival for Women Diagnosed With Cancer During Pregnancy or Lactation: A Registry-Based Cohort Study. JCO
27: 45-51
[Abstract][Full Text]
Tan, D. S.P., Rothermundt, C., Thomas, K., Bancroft, E., Eeles, R., Shanley, S., Ardern-Jones, A., Norman, A., Kaye, S. B., Gore, M. E.
(2008). "BRCAness" Syndrome in Ovarian Cancer: A Case-Control Study Describing the Clinical Features and Outcome of Patients With Epithelial Ovarian Cancer Associated With BRCA1 and BRCA2 Mutations. JCO
26: 5530-5536
[Abstract][Full Text]
Soegaard, M., Kjaer, S. K., Cox, M., Wozniak, E., Hogdall, E., Hogdall, C., Blaakaer, J., Jacobs, I. J., Gayther, S. A., Ramus, S. J.
(2008). BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark. Clin. Cancer Res.
14: 3761-3767
[Abstract][Full Text]
Kauff, N. D.
(2008). Is It Time to Stratify for BRCA Mutation Status in Therapeutic Trials in Ovarian Cancer?. JCO
26: 9-10
[Full Text]
Chetrit, A., Hirsh-Yechezkel, G., Ben-David, Y., Lubin, F., Friedman, E., Sadetzki, S.
(2008). Effect of BRCA1/2 Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer. JCO
26: 20-25
[Abstract][Full Text]
Cannistra, S. A.
(2007). BRCA-1 in Sporadic Epithelial Ovarian Cancer: Lessons Learned from the Genetics of Hereditary Disease. Clin. Cancer Res.
13: 7225-7227
[Full Text]
Quinn, J. E., James, C. R., Stewart, G. E., Mulligan, J. M., White, P., Chang, G. K.F., Mullan, P. B., Johnston, P. G., Wilson, R. H., Harkin, D. P.
(2007). BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy. Clin. Cancer Res.
13: 7413-7420
[Abstract][Full Text]
Risch, H. A., McLaughlin, J. R., Cole, D. E. C., Rosen, B., Bradley, L., Fan, I., Tang, J., Li, S., Zhang, S., Shaw, P. A., Narod, S. A.
(2006). Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada. JNCI J Natl Cancer Inst
98: 1694-1706
[Abstract][Full Text]
Plevritis, S. K., Kurian, A. W., Sigal, B. M., Daniel, B. L., Ikeda, D. M., Stockdale, F. E., Garber, A. M.
(2006). Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.. JAMA
295: 2374-2384
[Abstract][Full Text]
Sowter, H. M., Ashworth, A.
(2005). BRCA1 and BRCA2 as ovarian cancer susceptibility genes. Carcinogenesis
26: 1651-1656
[Abstract][Full Text]
Hartmann, L. C., Lu, K. H., Linette, G. P., Cliby, W. A., Kalli, K. R., Gershenson, D., Bast, R. C., Stec, J., Iartchouk, N., Smith, D. I., Ross, J. S., Hoersch, S., Shridhar, V., Lillie, J., Kaufmann, S. H., Clark, E. A., Damokosh, A. I.
(2005). Gene Expression Profiles Predict Early Relapse in Ovarian Cancer after Platinum-Paclitaxel Chemotherapy. Clin. Cancer Res.
11: 2149-2155
[Abstract][Full Text]
Cannistra, S. A.
(2004). Cancer of the Ovary. NEJM
351: 2519-2529
[Full Text]
Kirchhoff, T., Kauff, N. D., Mitra, N., Nafa, K., Huang, H., Palmer, C., Gulati, T., Wadsworth, E., Donat, S., Robson, M. E., Ellis, N. A., Offit, K.
(2004). BRCA Mutations and Risk of Prostate Cancer in Ashkenazi Jews. Clin. Cancer Res.
10: 2918-2921
[Abstract][Full Text]
Lakhani, S. R., Manek, S., Penault-Llorca, F., Flanagan, A., Arnout, L., Merrett, S., McGuffog, L., Steele, D., Devilee, P., Klijn, J. G. M., Meijers-Heijboer, H., Radice, P., Pilotti, S., Nevanlinna, H., Butzow, R., Sobol, H., Jacquemier, J., Lyonet, D. S., Neuhausen, S. L., Weber, B., Wagner, T., Winqvist, R., Bignon, Y.-J., Monti, F., Schmitt, F., Lenoir, G., Seitz, S., Hamman, U., Pharoah, P., Lane, G., Ponder, B., Bishop, D. T., Easton, D. F.
(2004). Pathology of Ovarian Cancers in BRCA1 and BRCA2 Carriers. Clin. Cancer Res.
10: 2473-2481
[Abstract][Full Text]
Pautier, P., Morice, P., Delaloge, S., Bressac-de Paillerets, B., Spatz, A.
(2004). Is Systemic Disease in the Coelomic Epithelium Associated With BRCA1 Germline Mutations?. JNCI J Natl Cancer Inst
96: 488-489
[Full Text]
Armstrong, K., Schwartz, J. S., Randall, T., Rubin, S. C., Weber, B.
(2004). Hormone Replacement Therapy and Life Expectancy After Prophylactic Oophorectomy in Women With BRCA1/2 Mutations: A Decision Analysis. JCO
22: 1045-1054
[Abstract][Full Text]
Modugno, F.
(2004). Ovarian Cancer and Polymorphisms in the Androgen and Progesterone Receptor Genes: A HuGE Review. Am J Epidemiol
159: 319-335
[Abstract][Full Text]
Levine, D. A., Argenta, P. A., Yee, C. J., Marshall, D. S., Olvera, N., Bogomolniy, F., Rahaman, J. A., Robson, M. E., Offit, K., Barakat, R. R., Soslow, R. A., Boyd, J.
(2003). Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations. JCO
21: 4222-4227
[Abstract][Full Text]
Dalpe, R., Bouchard, L., Houle, A.-J., Bedard, L.
(2003). Watching the Race to Find the Breast Cancer Genes. Science Technology Human Values
28: 187-216
[Abstract]
Ramus, S. J., Pharoah, P. D. P., Harrington, P., Pye, C., Werness, B., Bobrow, L., Ayhan, A., Wells, D., Fishman, A., Gore, M., DiCioccio, R. A., Piver, M. S., Whittemore, A. S., Ponder, B. A. J., Gayther, S. A.
(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.
(2003). Evidence-based management options for women at increased breast/ovarian cancer risk. Ann Oncol
14: 9-19
[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]
Buller, R. E., Shahin, M. S., Geisler, J. P., Zogg, M., De Young, B. R., Davis, C. S.
(2002). Failure of BRCA1 Dysfunction to Alter Ovarian Cancer Survival. Clin. Cancer Res.
8: 1196-1202
[Abstract][Full Text]
van Roosmalen, M. S., Verhoef, L. C.G., Stalmeier, P. F.M., Hoogerbrugge, N., van Daal, W. A.J.
(2002). Decision Analysis of Prophylactic Surgery or Screening for BRCA1 Mutation Carriers: A More Prominent Role For Oophorectomy. JCO
20: 2092-2100
[Abstract][Full Text]
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
20: 463-466
[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]
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]
