Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer

被引：527

作者：

Bolton, Kelly L. ^{[3
,4
]}

Chenevix-Trench, Georgia ^{[5
]}

Goh, Cindy ^{[6
]}

Sadetzki, Siegal ^{[7
,8
]}

Ramus, Susan J. ^{[9
]}

Karlan, Beth Y. ^{[10
]}

Lambrechts, Diether ^{[11
]}

Despierre, Evelyn ^{[12
]}

Barrowdale, Daniel ^{[13
]}

McGuffog, Lesley ^{[13
]}

Healey, Sue ^{[5
]}

Easton, Douglas F. ^{[13
]}

Sinilnikova, Olga ^{[14
,15
]}

Benitez, Javier ^{[17
,18
,19
]}

Garcia, Maria J. ^{[16
,19
]}

Neuhausen, Susan ^{[20
]}

Gail, Mitchell H. ^{[3
]}

Hartge, Patricia ^{[3
]}

Peock, Susan ^{[13
]}

Frost, Debra ^{[13
]}

Evans, Gareth ^{[21
]}

Eeles, Rosalind ^{[22
,23
]}

Godwin, Andrew K. ^{[24
]}

Daly, Mary B. ^{[25
]}

Kwong, Ava ^{[26
,28
]}

Ma, Edmond S. K. ^{[26
,27
]}

Lazaro, Conxi ^{[29
]}

Blanco, Ignacio ^{[29
]}

Montagna, Marco ^{[30
]}

D'Andrea, Emma ^{[32
]}

Nicoletto, Maria Ornella ^{[31
]}

Johnatty, Sharon E. ^{[5
]}

Krueger, Susanne ^{[33
,34
]}

Jensen, Allan ^{[33
,34
]}

Hogdall, Estrid ^{[33
,34
]}

Goode, Ellen L. ^{[35
]}

Fridley, Brooke L. ^{[35
]}

Loud, Jennifer T. ^{[36
]}

Greene, Mark H. ^{[36
]}

Mai, Phuong L. ^{[36
]}

Chetrit, Angela ^{[7
]}

Lubin, Flora ^{[7
]}

Hirsh-Yechezkel, Galit ^{[7
]}

Glendon, Gord ^{[37
]}

Andrulis, Irene L. ^{[37
,38
]}

Toland, Amanda E. ^{[39
,40
,41
]}

Senter, Leigha ^{[42
]}

Gore, Martin E. ^{[43
]}

Gourley, Charlie ^{[44
]}

Michie, Caroline O. ^{[44
]}

机构：

[1] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Canc Res United Kingdom, Cambridge CB1 8RN, England

[2] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[3] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[5] Univ Queensland, Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld, Australia

[6] Addenbrookes Hosp, Cambridge, England

[7] Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel

[8] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel

[9] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[10] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[11] Univ Leuven, VIB Vesalius Res Ctr, Louvain, Belgium

[12] Univ Leuven, Univ Hosp Leuven, Dept Obstet & Gynaecol, Louvain, Belgium

[13] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[14] Hosp Civils Lyon, Ctr Leon Berard, Unit Genet Predisposit Common Canc, Lyon, France

[15] Univ Lyon 1, INSERM, CNRS, Canc Res Ctr Lyon,U0152,UMR5286, F-69365 Lyon, France

[16] Human Genet Grp, Madrid, Spain

[17] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain

[18] Spanish Natl Canc Res Ctr, Genotyping Unit, Madrid, Spain

[19] CIBERER, Madrid, Spain

[20] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA

[21] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, England

[22] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England

[23] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England

[24] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, MO USA

[25] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA

[26] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China

[27] Hong Kong Sanat & Hosp, Div Mol Pathol, Hong Kong, Hong Kong, Peoples R China

[28] Univ Hong Kong, Queen Mary Hosp, Div Breast Surg, Hong Kong, Hong Kong, Peoples R China

[29] LHospitalet, Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain

[30] Ist Oncol Veneto IRCCS, Immunol & Mol Oncol Unit, Padua, Italy

[31] Ist Oncol Veneto IRCCS, Med Oncol Unit 1, Padua, Italy

[32] Ist Oncol Veneto IOV IRCCS, Dept Oncol & Surg Sci, Padua, Italy

[33] Univ Copenhagen, Rigshosp, Dept Virus Hormones & Canc, Danish Canc Soc, DK-2100 Copenhagen, Denmark

[34] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark

[35] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA

[36] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[37] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada

[38] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[39] Ohio State Univ, Comprehens Canc Ctr, Dept Internal Med & Mol Virol, Columbus, OH 43210 USA

[40] Ohio State Univ, Comprehens Canc Ctr, Dept Immunol, Columbus, OH 43210 USA

[41] Ohio State Univ, Comprehens Canc Ctr, Dept Med Genet, Columbus, OH 43210 USA

[42] Ohio State Univ, Comprehens Canc Ctr, Dept Internal Med, Clin Canc Genet Program, Columbus, OH 43210 USA

[43] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England

[44] Univ Edinburgh, Canc Res Ctr, Inst Genet & Mol Med, Western Gen Hosp, Edinburgh, Midlothian, Scotland

[45] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA

[46] Lund Univ, Dept Oncol, Lund, Sweden

[47] Univ & Reg Lab Skane, Dept Clin Genet, Lund, Sweden

[48] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA

[49] Univ Calif San Francisco, Canc Risk Program, San Francisco, CA 94143 USA

[50] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2012年 / 307卷 / 04期

基金：

美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会;

关键词：

BREAST-CANCER; PROGESTERONE-RECEPTOR; LOW-GRADE; NONSENSE; RISK; CARCINOMAS; POLYMERASE; CONSORTIUM; PATHOLOGY; FEATURES;

D O I：

10.1001/jama.2012.20

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390

引用

页码：382 / 390

页数：9

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