Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: A prospective cohort study

Susan M. Domchek, Tara M. Friebel, Susan L. Neuhausen, Theresa Wagner, Gareth Evans, Claudine Isaacs, Judy E. Garber, Mary B. Daly, Rosalind Eeles, Ellen Matloff, Gail E. Tomlinson, Laura Van't Veer, Henry T. Lynch, Olufunmilayo I. Olopade, Barbara L. Weber, Timothy R. Rebbeck

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Abstract

Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers. Methods: We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year. Findings: In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95% CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95% CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality. Interpretation: If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalThe Lancet Oncology
Volume7
Issue number3
DOIs
StatePublished - Mar 2006

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Ovariectomy
Cohort Studies
Prospective Studies
Mutation
Mortality
Ovarian Neoplasms
Neoplasms
Breast Neoplasms
Survival
Germ-Line Mutation
Genetic Testing
Risk Reduction Behavior

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Domchek, S. M., Friebel, T. M., Neuhausen, S. L., Wagner, T., Evans, G., Isaacs, C., ... Rebbeck, T. R. (2006). Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: A prospective cohort study. The Lancet Oncology, 7(3), 223-229. https://doi.org/10.1016/S1470-2045(06)70585-X

Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers : A prospective cohort study. / Domchek, Susan M.; Friebel, Tara M.; Neuhausen, Susan L.; Wagner, Theresa; Evans, Gareth; Isaacs, Claudine; Garber, Judy E.; Daly, Mary B.; Eeles, Rosalind; Matloff, Ellen; Tomlinson, Gail E.; Van't Veer, Laura; Lynch, Henry T.; Olopade, Olufunmilayo I.; Weber, Barbara L.; Rebbeck, Timothy R.

In: The Lancet Oncology, Vol. 7, No. 3, 03.2006, p. 223-229.

Research output: Contribution to journalArticle

Domchek, SM, Friebel, TM, Neuhausen, SL, Wagner, T, Evans, G, Isaacs, C, Garber, JE, Daly, MB, Eeles, R, Matloff, E, Tomlinson, GE, Van't Veer, L, Lynch, HT, Olopade, OI, Weber, BL & Rebbeck, TR 2006, 'Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: A prospective cohort study', The Lancet Oncology, vol. 7, no. 3, pp. 223-229. https://doi.org/10.1016/S1470-2045(06)70585-X
Domchek, Susan M. ; Friebel, Tara M. ; Neuhausen, Susan L. ; Wagner, Theresa ; Evans, Gareth ; Isaacs, Claudine ; Garber, Judy E. ; Daly, Mary B. ; Eeles, Rosalind ; Matloff, Ellen ; Tomlinson, Gail E. ; Van't Veer, Laura ; Lynch, Henry T. ; Olopade, Olufunmilayo I. ; Weber, Barbara L. ; Rebbeck, Timothy R. / Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers : A prospective cohort study. In: The Lancet Oncology. 2006 ; Vol. 7, No. 3. pp. 223-229.
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abstract = "Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers. Methods: We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year. Findings: In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95{\%} CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95{\%} CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality. Interpretation: If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.",
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T1 - Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers

T2 - A prospective cohort study

AU - Domchek, Susan M.

AU - Friebel, Tara M.

AU - Neuhausen, Susan L.

AU - Wagner, Theresa

AU - Evans, Gareth

AU - Isaacs, Claudine

AU - Garber, Judy E.

AU - Daly, Mary B.

AU - Eeles, Rosalind

AU - Matloff, Ellen

AU - Tomlinson, Gail E.

AU - Van't Veer, Laura

AU - Lynch, Henry T.

AU - Olopade, Olufunmilayo I.

AU - Weber, Barbara L.

AU - Rebbeck, Timothy R.

PY - 2006/3

Y1 - 2006/3

N2 - Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers. Methods: We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year. Findings: In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95% CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95% CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality. Interpretation: If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.

AB - Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers. Methods: We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year. Findings: In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95% CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95% CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality. Interpretation: If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.

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