This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (164)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Oncology  • Ovarian Cancer  • Genetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Jeff Boyd, PhD; Yukio Sonoda, MD; Mark G. Federici, MS; Faina Bogomolniy, BS; Esther Rhei, MD; Diane L. Maresco, PhD; Patricia E. Saigo, MD; Lois A. Almadrones, RN; Richard R. Barakat, MD; Carol L. Brown, MD; Dennis S. Chi, MD; John P. Curtin, MD; Elizabeth A. Poynor, MD; William J. Hoskins, MD

JAMA. 2000;283:2260-2265.

Context  Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival.

Objective  To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers.

Design and Setting  Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998).

Patients  The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison.

Main Outcome Measures  Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (III and IV) cases.

Results  Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03).

Conclusions  Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Author Affiliations: Departments of Surgery (Drs Boyd, Sonoda, Rhei, Maresco, Barakat, Brown, Chi, Curtin, Poynor, and Hoskins, Mr Federici, and Mss Bogomolniy and Almadrones), Human Genetics (Dr Boyd), and Pathology (Dr Saigo), Memorial Sloan-Kettering Cancer Center, New York, NY.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

May 3, 2000
JAMA. 2000;283(17):2317-2318.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Influence of Ovarian Cancer Risk Status on the Diagnostic Performance of the Serum Biomarkers Mesothelin, HE4, and CA125
Shah et al.
Cancer Epidemiol. Biomarkers Prev. 2009;18:1365-1372.
ABSTRACT | FULL TEXT  

BRCA Germline Mutations in Jewish Patients With Pancreatic Adenocarcinoma
Ferrone et al.
JCO 2009;27:433-438.
ABSTRACT | FULL TEXT  

Effect of BRCA1 Haplotype on Survival of Non-Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy
Kim et al.
JCO 2008;26:5972-5979.
ABSTRACT | FULL TEXT  

"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
Tan et al.
JCO 2008;26:5530-5536.
ABSTRACT | FULL TEXT  

Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology
Allain
J. Mol. Diagn. 2008;10:383-395.
ABSTRACT | FULL TEXT  

Sporadic Epithelial Ovarian Cancer: Clinical Relevance of BRCA1 Inhibition in the DNA Damage and Repair Pathway
Weberpals et al.
JCO 2008;26:3259-3267.
ABSTRACT | FULL TEXT  

BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark
Soegaard et al.
Clin. Cancer Res. 2008;14:3761-3767.
ABSTRACT | FULL TEXT  

Secondary BRCA1 Mutations in BRCA1-Mutated Ovarian Carcinomas with Platinum Resistance
Swisher et al.
Cancer Res. 2008;68:2581-2586.
ABSTRACT | FULL TEXT  

Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study
Kauff et al.
JCO 2008;26:1331-1337.
ABSTRACT | FULL TEXT  

Cancer surveillance based on imaging techniques in carriers of BRCA1/2 gene mutations: a systematic review
BERMEJO-PEREZ et al.
Br. J. Radiol. 2008;81:172-179.
ABSTRACT | FULL TEXT  

Is It Time to Stratify for BRCA Mutation Status in Therapeutic Trials in Ovarian Cancer?
Kauff
JCO 2008;26:9-10.
FULL TEXT  

Effect of BRCA1/2 Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer
Chetrit et al.
JCO 2008;26:20-25.
ABSTRACT | FULL TEXT  

BRCA-1 in Sporadic Epithelial Ovarian Cancer: Lessons Learned from the Genetics of Hereditary Disease
Cannistra
Clin. Cancer Res. 2007;13:7225-7227.
FULL TEXT  

BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy
Quinn et al.
Clin. Cancer Res. 2007;13:7413-7420.
ABSTRACT | FULL TEXT  

Modeling Genetic Risk of Breast Cancer
Kauff and Offit
JAMA 2007;297:2637-2639.
FULL TEXT  

Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation
DelloRusso et al.
Mol Cancer Res 2007;5:35-45.
ABSTRACT | FULL TEXT  

Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada
Risch et al.
JNCI J Natl Cancer Inst 2006;98:1694-1706.
ABSTRACT | FULL TEXT  

Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.
Plevritis et al.
JAMA 2006;295:2374-2384.
ABSTRACT | FULL TEXT  

BRCA1 and BRCA2 as ovarian cancer susceptibility genes
Sowter and Ashworth
Carcinogenesis 2005;26:1651-1656.
ABSTRACT | FULL TEXT  

Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System
Stirling et al.
JCO 2005;23:5588-5596.
ABSTRACT | FULL TEXT  

Gene Expression Profiles Predict Early Relapse in Ovarian Cancer after Platinum-Paclitaxel Chemotherapy
Hartmann et al.
Clin. Cancer Res. 2005;11:2149-2155.
ABSTRACT | FULL TEXT  

Prevention and Management of Hereditary Breast Cancer
Narod and Offit
JCO 2005;23:1656-1663.
FULL TEXT  

Hereditary Cancer Predisposition Syndromes
Garber and Offit
JCO 2005;23:276-292.
ABSTRACT | FULL TEXT  

Profiling the Perpetrator
Karlan
JCO 2004;22:4663-4664.
FULL TEXT  

Gene Expression Signature With Independent Prognostic Significance in Epithelial Ovarian Cancer
Spentzos et al.
JCO 2004;22:4700-4710.
ABSTRACT | FULL TEXT  

BRCA Mutations and Risk of Prostate Cancer in Ashkenazi Jews
Kirchhoff et al.
Clin. Cancer Res. 2004;10:2918-2921.
ABSTRACT | FULL TEXT  

Aggregation of Ovarian Cancer with Breast, Ovarian, Colorectal, and Prostate Cancer in First-degree Relatives
Tung et al.
Am J Epidemiol 2004;159:750-758.
ABSTRACT | FULL TEXT  

Pathology of Ovarian Cancers in BRCA1 and BRCA2 Carriers
Lakhani et al.
Clin. Cancer Res. 2004;10:2473-2481.
ABSTRACT | FULL TEXT  

Is Systemic Disease in the Coelomic Epithelium Associated With BRCA1 Germline Mutations?
Pautier et al.
JNCI J Natl Cancer Inst 2004;96:488-489.
FULL TEXT  

Ovarian Cancer and Polymorphisms in the Androgen and Progesterone Receptor Genes: A HuGE Review
Modugno
Am J Epidemiol 2004;159:319-335.
ABSTRACT | FULL TEXT  

Frequency of BRCA1 and BRCA2 Mutations in Unselected Ashkenazi Jewish Patients With Colorectal Cancer
Kirchhoff et al.
JNCI J Natl Cancer Inst 2004;96:68-70.
ABSTRACT | FULL TEXT  

BRCA1 functions as a breast stem cell regulator
Foulkes
J. Med. Genet. 2004;41:1-5.
ABSTRACT | FULL TEXT  

Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations
Levine et al.
JCO 2003;21:4222-4227.
ABSTRACT | FULL TEXT  

Ovarian Cancer Risk in Ashkenazi Jewish Carriers of BRCA1 and BRCA2 Mutations
Satagopan et al.
Clin. Cancer Res. 2002;8:3776-3781.
ABSTRACT | FULL TEXT  

Hereditary ovarian cancer resulting from a non-ovarian cancer cluster region (OCCR) BRCA2 mutation: is the OCCR useful clinically?
Al-Saffar and Foulkes
J. Med. Genet. 2002;39:e68-68.
FULL TEXT  

Methylation Profiles of Sporadic Ovarian Tumors and nonmalignant Ovaries from High-Risk Women
Rathi et al.
Clin. Cancer Res. 2002;8:3324-3331.
ABSTRACT | FULL TEXT  

Gene Expression Profiling of Hereditary and Sporadic Ovarian Cancers Reveals Unique BRCA1 and BRCA2 Signatures
Hedenfalk
JNCI J Natl Cancer Inst 2002;94:960-961.
FULL TEXT  

Gene Expression Profiles of BRCA1-Linked, BRCA2-Linked, and Sporadic Ovarian Cancers
Jazaeri et al.
JNCI J Natl Cancer Inst 2002;94:990-1000.
ABSTRACT | FULL TEXT  

Failure of BRCA1 Dysfunction to Alter Ovarian Cancer Survival
Buller et al.
Clin. Cancer Res. 2002;8:1196-1202.
ABSTRACT | FULL TEXT  

Clinical Characteristics of Individuals With Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals
Frank et al.
JCO 2002;20:1480-1490.
ABSTRACT | FULL TEXT  

Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers
Scheuer et al.
JCO 2002;20:1260-1268.
ABSTRACT | FULL TEXT  

Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors
Ben David et al.
JCO 2002;20:463-466.
ABSTRACT | FULL TEXT  

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
Sekine et al.
Clin. Cancer Res. 2001;7:3144-3150.
ABSTRACT | FULL TEXT  

The Androgen Receptor and Genetic Susceptibility to Ovarian Cancer: Results from a Case Series
Levine and Boyd
Cancer Res. 2001;61:908-911.
ABSTRACT | FULL TEXT  

Survival in Epithelial Ovarian Cancer Patients with Prior Breast Cancer
McGuire et al.
Am J Epidemiol 2000;152:528-532.
ABSTRACT | FULL TEXT  

BRCA-Linked and Sporadic Ovarian Cancer Are Clinically Comparable
JWatch Women's Health 2000;2000:10-10.
FULL TEXT  

*BRCA*-Linked and Sporadic Ovarian Cancer Are Clinically Comparable
JWatch General 2000;2000:1-1.
FULL TEXT