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- PMID: 22274685
- UKPMCID: 22274685
- DOI: 10.1001/jama.2012.20
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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; BenĂtez, Javier; GarcĂa, MarĂa J; Neuhausen, Susan; Gail, Mitchell H; Hartge, Patricia; Peock, Susan; Frost, Debra; Evans, D Gareth; Eeles, Rosalind; Godwin, Andrew K; Daly, Mary B; Kwong, Ava; Ma, Edmond S K; Lázaro, Conxi; Blanco, Ignacio; Montagna, Marco; D'Andrea, Emma; Nicoletto, Maria Ornella; Johnatty, Sharon E; Kjær, Susanne KrĂĽger; Jensen, Allan; Høgdall, 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, HĂĄkan; Borg, Ă…ke; 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; ; ;
JAMA. 2012;307(4):382-90.
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Full-text held externally
- PMID: 22274685
- UKPMCID: 22274685
- DOI: 10.1001/jama.2012.20
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 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.
Bibliographic metadata
- 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
- BenĂtez, Javier
- GarcĂa, MarĂa J
- Neuhausen, Susan
- Gail, Mitchell H
- Hartge, Patricia
- Peock, Susan
- Frost, Debra
- Evans, D Gareth
- Eeles, Rosalind
- Godwin, Andrew K
- Daly, Mary B
- Kwong, Ava
- Ma, Edmond S K
- Lázaro, Conxi
- Blanco, Ignacio
- Montagna, Marco
- D'Andrea, Emma
- Nicoletto, Maria Ornella
- Johnatty, Sharon E
- Kjær, Susanne Krüger
- Jensen, Allan
- Høgdall, 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, HĂĄkan
- Borg, Ă…ke
- 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
- 10118, Cancer Research UK, United Kingdom
- 11990, Cancer Research UK, United Kingdom
- 2P50 CA 058207, NCI NIH HHS, United States
- C1287/A10118, Cancer Research UK, United Kingdom
- C1287/A11990, Cancer Research UK, United Kingdom
- C490/A10119, Cancer Research UK, United Kingdom
- C490/A10124, Cancer Research UK, United Kingdom
- C5047/A8385, Cancer Research UK, United Kingdom
- CA 61126-03, NCI NIH HHS, United States
- CA 74415, NCI NIH HHS, United States
- K07 CA143047, NCI NIH HHS, United States
- N02-CP-11019-50, NCI NIH HHS, United States
- N02-CP-65504, NCI NIH HHS, United States
- P01 CA 130818, NCI NIH HHS, United States
- P50 CA 136393, NCI NIH HHS, United States
- R01 CA122443, NCI NIH HHS, United States
- R01-CA 122443, NCI NIH HHS, United States
- R01-CA 61107, NCI NIH HHS, United States
- SCD/11, Chief Scientist Office, United Kingdom
- , Chief Scientist Office, United Kingdom