Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

Francisco J Candido-dos-Reis; Honglin Song; Ellen L Goode; Julie M Cunningham; Brooke L Fridley; Melissa C Larson; Kathryn Alsop; Ed Dicks; Patricia Harrington; Susan J Ramus; Anna de Fazio; Gillian Mitchell; Sian Fereday; Kelly L Bolton; Charlie Gourley; Caroline Michie; Beth Karlan; Jenny Lester; Christine Walsh; Ilana Cass; Håkan Olsson; Martin Gore; Javier J Benitez; Maria J Garcia; Irene Andrulis; Anna Marie Mulligan; Gord Glendon; Ignacio Blanco; Conxi Lazaro; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Marco Montagna; Elisa Alducci; Siegal Sadetzki; Angela Chetrit; Ava Kwong; Susanne K Kjaer; Allan Jensen; Estrid Høgdall; Susan Neuhausen; Robert Nussbaum; Mary Daly; Mark H Greene; Phuong L Mai; Jennifer T Loud; Kirsten Moysich; Amanda E Toland; Diether Lambrechts; Steve Ellis; for EMBRACE

doi:10.1158/1078-0432.ccr-14-2497

Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

Francisco J Candido-dos-Reis, Honglin Song, Ellen L Goode, Julie M Cunningham, Brooke L Fridley, Melissa C Larson, Kathryn Alsop, Ed Dicks, Patricia Harrington, Susan J Ramus, Anna de Fazio, Gillian Mitchell, Sian Fereday, Kelly L Bolton, Charlie Gourley, Caroline Michie, Beth Karlan, Jenny Lester, Christine Walsh, Ilana CassHåkan Olsson, Martin Gore, Javier J Benitez, Maria J Garcia, Irene Andrulis, Anna Marie Mulligan, Gord Glendon, Ignacio Blanco, Conxi Lazaro, Alice S Whittemore, Valerie McGuire, Weiva Sieh, Marco Montagna, Elisa Alducci, Siegal Sadetzki, Angela Chetrit, Ava Kwong, Susanne K Kjaer, Allan Jensen, Estrid Høgdall, Susan Neuhausen, Robert Nussbaum, Mary Daly, Mark H Greene, Phuong L Mai, Jennifer T Loud, Kirsten Moysich, Amanda E Toland, Diether Lambrechts, Steve Ellis, for EMBRACE

86 Citations (Scopus)

Abstract

The authors thank Craig Luccarini, the staff at the Eastern Cancer Registration and Information Centre (SEARCH); Alicia Barroso, Victoria Fernandez, Miguel Urioste; Spanish Network on Rare Diseases (CIBERER); Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the Clinical Follow-Up Study Members, and the kConFab Investigators (Peter MacCallum Cancer Center, East Melbourne, Australia: Stephen Fox, MD; Ian Campbell, PhD; Melissa Brown, PhD; Gerda Evans; Judy Kirk: Westmead Hospital, MD, PhD; Sunil Lakhani, MD; Geoff Lindeman, MD, PhD; Gillian Mitchell, MD, PhD; Kelly Phillips, MD; Melanie Price, PhD; Christobel Saunders, MD; Mandy Spurdle, PhD; Graeme Suthers, MD, PhD; Roger Milne, PhD) (kConFab/AOCS); Nayana Weerasooriya, Teresa Selander. A full list of principal investigators and participating centers for EMBRACE has been published (Hum Mol Genet 2010;19:2886-97). Purpose: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. Experimental Design: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. Results: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.

Original language	English
Journal	Clinical Cancer Research
Volume	21
Issue number	3
Pages (from-to)	652-7
Number of pages	6
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.ccr-14-2497
Publication status	Published - 1 Feb 2015

Keywords

Aged
Female
Genes, BRCA1
Genes, BRCA2
Germ-Line Mutation
Humans
Middle Aged
Neoplasm Grading
Neoplasm Staging
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Prognosis
Survival Analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Candido-dos-Reis, F. J., Song, H., Goode, E. L., Cunningham, J. M., Fridley, B. L., Larson, M. C., Alsop, K., Dicks, E., Harrington, P., Ramus, S. J., de Fazio, A., Mitchell, G., Fereday, S., Bolton, K. L., Gourley, C., Michie, C., Karlan, B., Lester, J., Walsh, C., ... for EMBRACE (2015). Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clinical Cancer Research, 21(3), 652-7. https://doi.org/10.1158/1078-0432.ccr-14-2497

Candido-dos-Reis, FJ, Song, H, Goode, EL, Cunningham, JM, Fridley, BL, Larson, MC, Alsop, K, Dicks, E, Harrington, P, Ramus, SJ, de Fazio, A, Mitchell, G, Fereday, S, Bolton, KL, Gourley, C, Michie, C, Karlan, B, Lester, J, Walsh, C, Cass, I, Olsson, H, Gore, M, Benitez, JJ, Garcia, MJ, Andrulis, I, Mulligan, AM, Glendon, G, Blanco, I, Lazaro, C, Whittemore, AS, McGuire, V, Sieh, W, Montagna, M, Alducci, E, Sadetzki, S, Chetrit, A, Kwong, A, Kjaer, SK, Jensen, A, Høgdall, E, Neuhausen, S, Nussbaum, R, Daly, M, Greene, MH, Mai, PL, Loud, JT, Moysich, K, Toland, AE, Lambrechts, D, Ellis, S & for EMBRACE 2015, 'Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer', Clinical Cancer Research, vol. 21, no. 3, pp. 652-7. https://doi.org/10.1158/1078-0432.ccr-14-2497

@article{4822d0c7009a4fa686c94f43ce88df81,

title = "Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer",

abstract = "The authors thank Craig Luccarini, the staff at the Eastern Cancer Registration and Information Centre (SEARCH); Alicia Barroso, Victoria Fernandez, Miguel Urioste; Spanish Network on Rare Diseases (CIBERER); Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the Clinical Follow-Up Study Members, and the kConFab Investigators (Peter MacCallum Cancer Center, East Melbourne, Australia: Stephen Fox, MD; Ian Campbell, PhD; Melissa Brown, PhD; Gerda Evans; Judy Kirk: Westmead Hospital, MD, PhD; Sunil Lakhani, MD; Geoff Lindeman, MD, PhD; Gillian Mitchell, MD, PhD; Kelly Phillips, MD; Melanie Price, PhD; Christobel Saunders, MD; Mandy Spurdle, PhD; Graeme Suthers, MD, PhD; Roger Milne, PhD) (kConFab/AOCS); Nayana Weerasooriya, Teresa Selander. A full list of principal investigators and participating centers for EMBRACE has been published (Hum Mol Genet 2010;19:2886-97). Purpose: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. Experimental Design: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. Results: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.",

keywords = "Aged, Female, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, Humans, Middle Aged, Neoplasm Grading, Neoplasm Staging, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Prognosis, Survival Analysis",

author = "Candido-dos-Reis, {Francisco J} and Honglin Song and Goode, {Ellen L} and Cunningham, {Julie M} and Fridley, {Brooke L} and Larson, {Melissa C} and Kathryn Alsop and Ed Dicks and Patricia Harrington and Ramus, {Susan J} and {de Fazio}, Anna and Gillian Mitchell and Sian Fereday and Bolton, {Kelly L} and Charlie Gourley and Caroline Michie and Beth Karlan and Jenny Lester and Christine Walsh and Ilana Cass and H{\aa}kan Olsson and Martin Gore and Benitez, {Javier J} and Garcia, {Maria J} and Irene Andrulis and Mulligan, {Anna Marie} and Gord Glendon and Ignacio Blanco and Conxi Lazaro and Whittemore, {Alice S} and Valerie McGuire and Weiva Sieh and Marco Montagna and Elisa Alducci and Siegal Sadetzki and Angela Chetrit and Ava Kwong and Kjaer, {Susanne K} and Allan Jensen and Estrid H{\o}gdall and Susan Neuhausen and Robert Nussbaum and Mary Daly and Greene, {Mark H} and Mai, {Phuong L} and Loud, {Jennifer T} and Kirsten Moysich and Toland, {Amanda E} and Diether Lambrechts and Steve Ellis and {for EMBRACE}",

note = "{\textcopyright}2014 American Association for Cancer Research.",

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doi = "10.1158/1078-0432.ccr-14-2497",

language = "English",

volume = "21",

pages = "652--7",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research (A A C R)",

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TY - JOUR

T1 - Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

AU - Candido-dos-Reis, Francisco J

AU - Song, Honglin

AU - Goode, Ellen L

AU - Cunningham, Julie M

AU - Fridley, Brooke L

AU - Larson, Melissa C

AU - Alsop, Kathryn

AU - Dicks, Ed

AU - Harrington, Patricia

AU - Ramus, Susan J

AU - de Fazio, Anna

AU - Mitchell, Gillian

AU - Fereday, Sian

AU - Bolton, Kelly L

AU - Gourley, Charlie

AU - Michie, Caroline

AU - Karlan, Beth

AU - Lester, Jenny

AU - Walsh, Christine

AU - Cass, Ilana

AU - Olsson, Håkan

AU - Gore, Martin

AU - Benitez, Javier J

AU - Garcia, Maria J

AU - Andrulis, Irene

AU - Mulligan, Anna Marie

AU - Glendon, Gord

AU - Blanco, Ignacio

AU - Lazaro, Conxi

AU - Whittemore, Alice S

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Montagna, Marco

AU - Alducci, Elisa

AU - Sadetzki, Siegal

AU - Chetrit, Angela

AU - Kwong, Ava

AU - Kjaer, Susanne K

AU - Jensen, Allan

AU - Høgdall, Estrid

AU - Neuhausen, Susan

AU - Nussbaum, Robert

AU - Daly, Mary

AU - Greene, Mark H

AU - Mai, Phuong L

AU - Loud, Jennifer T

AU - Moysich, Kirsten

AU - Toland, Amanda E

AU - Lambrechts, Diether

AU - Ellis, Steve

AU - for EMBRACE

PY - 2015/2/1

Y1 - 2015/2/1

N2 - The authors thank Craig Luccarini, the staff at the Eastern Cancer Registration and Information Centre (SEARCH); Alicia Barroso, Victoria Fernandez, Miguel Urioste; Spanish Network on Rare Diseases (CIBERER); Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the Clinical Follow-Up Study Members, and the kConFab Investigators (Peter MacCallum Cancer Center, East Melbourne, Australia: Stephen Fox, MD; Ian Campbell, PhD; Melissa Brown, PhD; Gerda Evans; Judy Kirk: Westmead Hospital, MD, PhD; Sunil Lakhani, MD; Geoff Lindeman, MD, PhD; Gillian Mitchell, MD, PhD; Kelly Phillips, MD; Melanie Price, PhD; Christobel Saunders, MD; Mandy Spurdle, PhD; Graeme Suthers, MD, PhD; Roger Milne, PhD) (kConFab/AOCS); Nayana Weerasooriya, Teresa Selander. A full list of principal investigators and participating centers for EMBRACE has been published (Hum Mol Genet 2010;19:2886-97). Purpose: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. Experimental Design: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. Results: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.

AB - The authors thank Craig Luccarini, the staff at the Eastern Cancer Registration and Information Centre (SEARCH); Alicia Barroso, Victoria Fernandez, Miguel Urioste; Spanish Network on Rare Diseases (CIBERER); Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the Clinical Follow-Up Study Members, and the kConFab Investigators (Peter MacCallum Cancer Center, East Melbourne, Australia: Stephen Fox, MD; Ian Campbell, PhD; Melissa Brown, PhD; Gerda Evans; Judy Kirk: Westmead Hospital, MD, PhD; Sunil Lakhani, MD; Geoff Lindeman, MD, PhD; Gillian Mitchell, MD, PhD; Kelly Phillips, MD; Melanie Price, PhD; Christobel Saunders, MD; Mandy Spurdle, PhD; Graeme Suthers, MD, PhD; Roger Milne, PhD) (kConFab/AOCS); Nayana Weerasooriya, Teresa Selander. A full list of principal investigators and participating centers for EMBRACE has been published (Hum Mol Genet 2010;19:2886-97). Purpose: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. Experimental Design: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. Results: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.

KW - Aged

KW - Female

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Germ-Line Mutation

KW - Humans

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Staging

KW - Neoplasms, Glandular and Epithelial

KW - Ovarian Neoplasms

KW - Prognosis

KW - Survival Analysis

U2 - 10.1158/1078-0432.ccr-14-2497

DO - 10.1158/1078-0432.ccr-14-2497

M3 - Journal article

C2 - 25398451

SN - 1078-0432

VL - 21

SP - 652

EP - 657

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 3

ER -

Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

Abstract

Keywords

UN SDGs

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