Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

Bolton, Kelly L., Chenevix-Trench, Georgia, Goh, Cindy, Sadetzki, Siegal, Ramus, Susan J., Karlan, Beth Y., Lambrechts, Diether, Despierre, Evelyn, Barrowdale, Daniel, McGuffog, Lesley, Healey, Sue, Easton, Douglas F., Sinilnikova, Olga, Benitez, Javier, Garcia, María J., Neuhausen, Susan, Gail, Mitchell H., Hartge, Patricia, Peock, Susan, Frost, Debra, Evans, Gareth, Eeles, Rosalind, Godwin, Andrew K., Daly, Mary B., Kwong, Ava, Ma, Edmond S. K., Lazaro, Conxi, Blanco, Ignacio, Montagna, Marco, D'Andrea, Emma, Nicoletto, Maria Ornella, Johnatty, Sharon E., Kruger, Susanne, Jensen, Allan, Hogdall, Estrid, Goode, Ellen L., Fridley, Brooke L., Loud, Jennifer T., Greene, Mark H., Mai, Phuong L., Chetrit, Angela, Lubin, Flora, Hirsh-Yechezkel, Galit, Glendon, Gord, Andrulis, Irene L., Toland, Amanda E., Senter, Leigha, Gore, Martin E., Gourley, Charlie, Michie, Caroline O., Song, Honglin, Tyrer, Jonathan, Whittemore, Alice S., McGuire, Valerie, Sieh, Weiva, Kristoffersson, Ulf, Olsson, Håkan, Borg, Åke, Levine, Douglas A., Steele, Linda, Beattie, Mary S., Chan, Salina, Nussbaum, Robert L., Moysich, Kirsten B., Gross, Jenny, Cass, Ilana, Walsh, Christine, Li, Andrew J., Leuchter, Ronald, Gordon, Ora, Garcia-Closas, Montserrat, Gayther, Simon A., Chanock, Stephen J., Antoniou, Antonis C., Pharoah, Paul D. P., EMBRACE, kConFab Investigators and Cancer Genome Atlas Research Network (2012) Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. Jama-Journal of the American Medical Association, 307 4: 382-390.

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Author Bolton, Kelly L.
Chenevix-Trench, Georgia
Goh, Cindy
Sadetzki, Siegal
Ramus, Susan J.
Karlan, Beth Y.
Lambrechts, Diether
Despierre, Evelyn
Barrowdale, Daniel
McGuffog, Lesley
Healey, Sue
Easton, Douglas F.
Sinilnikova, Olga
Benitez, Javier
Garcia, María J.
Neuhausen, Susan
Gail, Mitchell H.
Hartge, Patricia
Peock, Susan
Frost, Debra
Evans, Gareth
Eeles, Rosalind
Godwin, Andrew K.
Daly, Mary B.
Kwong, Ava
Ma, Edmond S. K.
Lazaro, Conxi
Blanco, Ignacio
Montagna, Marco
D'Andrea, Emma
Nicoletto, Maria Ornella
Johnatty, Sharon E.
Kruger, Susanne
Jensen, Allan
Hogdall, Estrid
Goode, Ellen L.
Fridley, Brooke L.
Loud, Jennifer T.
Greene, Mark H.
Mai, Phuong L.
Chetrit, Angela
Lubin, Flora
Hirsh-Yechezkel, Galit
Glendon, Gord
Andrulis, Irene L.
Toland, Amanda E.
Senter, Leigha
Gore, Martin E.
Gourley, Charlie
Michie, Caroline O.
Song, Honglin
Tyrer, Jonathan
Whittemore, Alice S.
McGuire, Valerie
Sieh, Weiva
Kristoffersson, Ulf
Olsson, Håkan
Borg, Åke
Levine, Douglas A.
Steele, Linda
Beattie, Mary S.
Chan, Salina
Nussbaum, Robert L.
Moysich, Kirsten B.
Gross, Jenny
Cass, Ilana
Walsh, Christine
Li, Andrew J.
Leuchter, Ronald
Gordon, Ora
Garcia-Closas, Montserrat
Gayther, Simon A.
Chanock, Stephen J.
Antoniou, Antonis C.
Pharoah, Paul D. P.
EMBRACE
kConFab Investigators
Cancer Genome Atlas Research Network
Total Author Count Override 75
Title Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer
Journal name Jama-Journal of the American Medical Association   Check publisher's open access policy
ISSN 0098-7484
1538-3598
Publication date 2012-01
Sub-type Article (original research)
DOI 10.1001/jama.2012.20
Volume 307
Issue 4
Start page 382
End page 390
Total pages 9
Place of publication Chicago, IL, United States
Publisher American Medical Association
Collection year 2013
Language eng
Formatted abstract 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 amore 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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