Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer

Kelly L. Bolton, Georgia Chenevix-Trench, Cindy Goh, Siegal Sadetzki, Susan J. Ramus, Beth Y. Karlan, Diether Lambrechts, Evelyn Despierre, Daniel Barrowdale, Lesley McGuffog, Sue Healey, Douglas F. Easton, Olga Sinilnikova, Javier Benítez, María J. García, Susan Neuhausen, Mitchell H. Gail, Patricia Hartge, Susan Peock, Debra FrostD. Gareth Evans, Rosalind Eeles, Andrew K. Godwin, Mary B. Daly, Ava Kwong, Edmond S K Ma, Conxi Lázaro, Ignacio Blanco, Marco Montagna, Emma D'Andrea, Maria Ornella Nicoletto, Sharon E. Johnatty, Susanne Krüger Kjær, Allan Jensen, Estrid Høgdall, Ellen L Goode, Brooke L. Fridley, Jennifer T. Loud, Mark H. Greene, Phuong L. Mai, Angela Chetrit, Flora Lubin, Galit Hirsh-Yechezkel, Gord Glendon, Irene L. Andrulis, Amanda E. Toland, Leigha Senter, Martin E. Gore, Charlie Gourley, Caroline O. Michie, Honglin Song, Jonathan Tyrer, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Ulf Kristoffersson, Håkan Olsson, Åke Borg, Douglas A. Levine, Linda Steele, Mary S. Beattie, Salina Chan, Robert L. Nussbaum, Kirsten B. Moysich, Jenny Gross, Ilana Cass, Christine Walsh, Andrew J. Li, Ronald Leuchter, Ora Gordon, Montserrat Garcia-Closas, Simon A. Gayther, Stephen J. Chanock, Antonis C. Antoniou, Paul D P Pharoah

Research output: Contribution to journalArticle

319 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)382-390
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number4
DOIs
StatePublished - Jan 25 2012

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Mutation
Survival
Germ-Line Mutation
Ovarian epithelial cancer
Ovarian Neoplasms
Observational Studies
Histology
Outcome Assessment (Health Care)
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bolton, K. L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S. J., Karlan, B. Y., ... Pharoah, P. D. P. (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. https://doi.org/10.1001/jama.2012.20

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; Benítez, Javier; García, María 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, 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.

In: JAMA - Journal of the American Medical Association, Vol. 307, No. 4, 25.01.2012, p. 382-390.

Research output: Contribution to journalArticle

Bolton, KL, Chenevix-Trench, G, Goh, C, Sadetzki, S, Ramus, SJ, Karlan, BY, Lambrechts, D, Despierre, E, Barrowdale, D, McGuffog, L, Healey, S, Easton, DF, Sinilnikova, O, Benítez, J, García, MJ, Neuhausen, S, Gail, MH, Hartge, P, Peock, S, Frost, D, Evans, DG, Eeles, R, Godwin, AK, Daly, MB, Kwong, A, Ma, ESK, Lázaro, C, Blanco, I, Montagna, M, D'Andrea, E, Nicoletto, MO, Johnatty, SE, Kjær, SK, Jensen, A, Høgdall, E, Goode, EL, Fridley, BL, Loud, JT, Greene, MH, Mai, PL, Chetrit, A, Lubin, F, Hirsh-Yechezkel, G, Glendon, G, Andrulis, IL, Toland, AE, Senter, L, Gore, ME, Gourley, C, Michie, CO, Song, H, Tyrer, J, Whittemore, AS, McGuire, V, Sieh, W, Kristoffersson, U, Olsson, H, Borg, Å, Levine, DA, Steele, L, Beattie, MS, Chan, S, Nussbaum, RL, Moysich, KB, Gross, J, Cass, I, Walsh, C, Li, AJ, Leuchter, R, Gordon, O, Garcia-Closas, M, Gayther, SA, Chanock, SJ, Antoniou, AC & Pharoah, PDP 2012, 'Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer', JAMA - Journal of the American Medical Association, vol. 307, no. 4, pp. 382-390. https://doi.org/10.1001/jama.2012.20
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 ; Benítez, Javier ; García, María 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, 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. / Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 307, No. 4. pp. 382-390.
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title = "Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer",
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.",
author = "Bolton, {Kelly L.} and Georgia Chenevix-Trench and Cindy Goh and Siegal Sadetzki and Ramus, {Susan J.} and Karlan, {Beth Y.} and Diether Lambrechts and Evelyn Despierre and Daniel Barrowdale and Lesley McGuffog and Sue Healey and Easton, {Douglas F.} and Olga Sinilnikova and Javier Ben{\'i}tez and Garc{\'i}a, {Mar{\'i}a J.} and Susan Neuhausen and Gail, {Mitchell H.} and Patricia Hartge and Susan Peock and Debra Frost and Evans, {D. Gareth} and Rosalind Eeles and Godwin, {Andrew K.} and Daly, {Mary B.} and Ava Kwong and Ma, {Edmond S K} and Conxi L{\'a}zaro and Ignacio Blanco and Marco Montagna and Emma D'Andrea and Nicoletto, {Maria Ornella} and Johnatty, {Sharon E.} and Kj{\ae}r, {Susanne Kr{\"u}ger} and Allan Jensen and Estrid H{\o}gdall and Goode, {Ellen L} and Fridley, {Brooke L.} and Loud, {Jennifer T.} and Greene, {Mark H.} and Mai, {Phuong L.} and Angela Chetrit and Flora Lubin and Galit Hirsh-Yechezkel and Gord Glendon and Andrulis, {Irene L.} and Toland, {Amanda E.} and Leigha Senter and Gore, {Martin E.} and Charlie Gourley and Michie, {Caroline O.} and Honglin Song and Jonathan Tyrer and Whittemore, {Alice S.} and Valerie McGuire and Weiva Sieh and Ulf Kristoffersson and H{\aa}kan Olsson and {\AA}ke Borg and Levine, {Douglas A.} and Linda Steele and Beattie, {Mary S.} and Salina Chan and Nussbaum, {Robert L.} and Moysich, {Kirsten B.} and Jenny Gross and Ilana Cass and Christine Walsh and Li, {Andrew J.} and Ronald Leuchter and Ora Gordon and Montserrat Garcia-Closas and Gayther, {Simon A.} and Chanock, {Stephen J.} and Antoniou, {Antonis C.} and Pharoah, {Paul D P}",
year = "2012",
month = "1",
day = "25",
doi = "10.1001/jama.2012.20",
language = "English (US)",
volume = "307",
pages = "382--390",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "4",

}

TY - JOUR

T1 - Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer

AU - Bolton, Kelly L.

AU - Chenevix-Trench, Georgia

AU - Goh, Cindy

AU - Sadetzki, Siegal

AU - Ramus, Susan J.

AU - Karlan, Beth Y.

AU - Lambrechts, Diether

AU - Despierre, Evelyn

AU - Barrowdale, Daniel

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Easton, Douglas F.

AU - Sinilnikova, Olga

AU - Benítez, Javier

AU - García, María J.

AU - Neuhausen, Susan

AU - Gail, Mitchell H.

AU - Hartge, Patricia

AU - Peock, Susan

AU - Frost, Debra

AU - Evans, D. Gareth

AU - Eeles, Rosalind

AU - Godwin, Andrew K.

AU - Daly, Mary B.

AU - Kwong, Ava

AU - Ma, Edmond S K

AU - Lázaro, Conxi

AU - Blanco, Ignacio

AU - Montagna, Marco

AU - D'Andrea, Emma

AU - Nicoletto, Maria Ornella

AU - Johnatty, Sharon E.

AU - Kjær, Susanne Krüger

AU - Jensen, Allan

AU - Høgdall, Estrid

AU - Goode, Ellen L

AU - Fridley, Brooke L.

AU - Loud, Jennifer T.

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Chetrit, Angela

AU - Lubin, Flora

AU - Hirsh-Yechezkel, Galit

AU - Glendon, Gord

AU - Andrulis, Irene L.

AU - Toland, Amanda E.

AU - Senter, Leigha

AU - Gore, Martin E.

AU - Gourley, Charlie

AU - Michie, Caroline O.

AU - Song, Honglin

AU - Tyrer, Jonathan

AU - Whittemore, Alice S.

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Kristoffersson, Ulf

AU - Olsson, Håkan

AU - Borg, Åke

AU - Levine, Douglas A.

AU - Steele, Linda

AU - Beattie, Mary S.

AU - Chan, Salina

AU - Nussbaum, Robert L.

AU - Moysich, Kirsten B.

AU - Gross, Jenny

AU - Cass, Ilana

AU - Walsh, Christine

AU - Li, Andrew J.

AU - Leuchter, Ronald

AU - Gordon, Ora

AU - Garcia-Closas, Montserrat

AU - Gayther, Simon A.

AU - Chanock, Stephen J.

AU - Antoniou, Antonis C.

AU - Pharoah, Paul D P

PY - 2012/1/25

Y1 - 2012/1/25

N2 - 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.

AB - 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.

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U2 - 10.1001/jama.2012.20

DO - 10.1001/jama.2012.20

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AN - SCOPUS:84856158117

VL - 307

SP - 382

EP - 390

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

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