Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer

A multicenter, prospective study

Noah D. Kauff, Susan M. Domchek, Tara M. Friebel, Mark E. Robson, Johanna Lee, Judy E. Garber, Claudine Isaacs, D. Gareth Evans, Henry T. Lynch, Rosalind A. Eeles, Susan L. Neuhausen, Mary B. Daly, Ellen Matloff, Joanne L. Blum, Paul Sabbatini, Richard R. Barakat, Clifford Hudis, Larry Norton, Kenneth Offit, Timothy R. Rebbeck

Research output: Contribution to journalArticle

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Abstract

Purpose: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

Original languageEnglish
Pages (from-to)1331-1337
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number8
DOIs
StatePublished - Mar 10 2008

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Ovariectomy
Multicenter Studies
Prospective Studies
Breast Neoplasms
Mutation
Risk Reduction Behavior
Neoplasms
Breast
Odds Ratio
Fallopian Tubes
Proportional Hazards Models
Medical Records
Ovary
Observation
Genes

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer : A multicenter, prospective study. / Kauff, Noah D.; Domchek, Susan M.; Friebel, Tara M.; Robson, Mark E.; Lee, Johanna; Garber, Judy E.; Isaacs, Claudine; Evans, D. Gareth; Lynch, Henry T.; Eeles, Rosalind A.; Neuhausen, Susan L.; Daly, Mary B.; Matloff, Ellen; Blum, Joanne L.; Sabbatini, Paul; Barakat, Richard R.; Hudis, Clifford; Norton, Larry; Offit, Kenneth; Rebbeck, Timothy R.

In: Journal of Clinical Oncology, Vol. 26, No. 8, 10.03.2008, p. 1331-1337.

Research output: Contribution to journalArticle

Kauff, ND, Domchek, SM, Friebel, TM, Robson, ME, Lee, J, Garber, JE, Isaacs, C, Evans, DG, Lynch, HT, Eeles, RA, Neuhausen, SL, Daly, MB, Matloff, E, Blum, JL, Sabbatini, P, Barakat, RR, Hudis, C, Norton, L, Offit, K & Rebbeck, TR 2008, 'Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: A multicenter, prospective study', Journal of Clinical Oncology, vol. 26, no. 8, pp. 1331-1337. https://doi.org/10.1200/JCO.2007.13.9626
Kauff, Noah D. ; Domchek, Susan M. ; Friebel, Tara M. ; Robson, Mark E. ; Lee, Johanna ; Garber, Judy E. ; Isaacs, Claudine ; Evans, D. Gareth ; Lynch, Henry T. ; Eeles, Rosalind A. ; Neuhausen, Susan L. ; Daly, Mary B. ; Matloff, Ellen ; Blum, Joanne L. ; Sabbatini, Paul ; Barakat, Richard R. ; Hudis, Clifford ; Norton, Larry ; Offit, Kenneth ; Rebbeck, Timothy R. / Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer : A multicenter, prospective study. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 8. pp. 1331-1337.
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abstract = "Purpose: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17{\%} to 39{\%} of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: During 3-year follow-up, RRSO was associated with an 85{\%} reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95{\%} CI, 0.04 to 0.56) and a 72{\%} reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95{\%} CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95{\%} CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95{\%} CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.",
author = "Kauff, {Noah D.} and Domchek, {Susan M.} and Friebel, {Tara M.} and Robson, {Mark E.} and Johanna Lee and Garber, {Judy E.} and Claudine Isaacs and Evans, {D. Gareth} and Lynch, {Henry T.} and Eeles, {Rosalind A.} and Neuhausen, {Susan L.} and Daly, {Mary B.} and Ellen Matloff and Blum, {Joanne L.} and Paul Sabbatini and Barakat, {Richard R.} and Clifford Hudis and Larry Norton and Kenneth Offit and Rebbeck, {Timothy R.}",
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T1 - Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer

T2 - A multicenter, prospective study

AU - Kauff, Noah D.

AU - Domchek, Susan M.

AU - Friebel, Tara M.

AU - Robson, Mark E.

AU - Lee, Johanna

AU - Garber, Judy E.

AU - Isaacs, Claudine

AU - Evans, D. Gareth

AU - Lynch, Henry T.

AU - Eeles, Rosalind A.

AU - Neuhausen, Susan L.

AU - Daly, Mary B.

AU - Matloff, Ellen

AU - Blum, Joanne L.

AU - Sabbatini, Paul

AU - Barakat, Richard R.

AU - Hudis, Clifford

AU - Norton, Larry

AU - Offit, Kenneth

AU - Rebbeck, Timothy R.

PY - 2008/3/10

Y1 - 2008/3/10

N2 - Purpose: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

AB - Purpose: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

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