Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: A multicenter, prospective study Journal Article


Authors: Kauff, N. D.; Domchek, S. M.; Friebel, T. M.; Robson, M. E.; Lee, J.; Garber, J. E.; Isaacs, C.; Evans, D. G.; Lynch, H.; Eeles, R. A.; Neuhausen, S. L.; Daly, M. B.; Matloff, E.; Blum, J. L.; Sabbatini, P.; Barakat, R. R.; Hudis, C.; Norton, L.; Offit, K.; Rebbeck, T. R.
Article Title: Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: A multicenter, prospective study
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. © 2008 by American Society of Clinical Oncology.
Keywords: adult; aged; aged, 80 and over; disease-free survival; middle aged; gene mutation; major clinical study; genetics; mutation; clinical trial; cancer risk; disease free survival; follow up; follow-up studies; prospective study; salpingooophorectomy; prospective studies; ovarian neoplasms; cancer prevention; breast cancer; ovariectomy; incidence; risk factors; breast neoplasms; risk factor; questionnaire; oncogene; tumor suppressor gene; genes, brca1; genes, brca2; multicenter study; breast tumor; ovary tumor; medical record; genetic risk; risk reduction; gynecologic cancer; germ-line mutation; risk reduction behavior; salpingostomy
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 8
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-03-10
Start Page: 1331
End Page: 1337
Language: English
DOI: 10.1200/jco.2007.13.9626
PUBMED: 18268356
PROVIDER: scopus
PMCID: PMC3306809
DOI/URL:
Notes: --- - "Cited By (since 1996): 112" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kenneth Offit
    507 Offit
  2. Richard R Barakat
    586 Barakat
  3. Clifford Hudis
    837 Hudis
  4. Larry Norton
    556 Norton
  5. Mark E Robson
    365 Robson
  6. Noah Kauff
    122 Kauff
  7. Paul J Sabbatini
    199 Sabbatini