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.

• Authors: Noah D Kauff, Susan M Domchek, Tara M Friebel, Mark E Robson, Johanna Lee, Judy E Garber, Claudine Isaacs, D Gareth Evans, Henry 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 8 Pg. 1331-7 (Mar 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18268356 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Topics

• Adult
• Aged
• Aged, 80 and over
• Breast Neoplasms (genetics, prevention & control)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Genes, BRCA1
• Genes, BRCA2
• Germ-Line Mutation
• Humans
• Incidence
• Middle Aged
• Ovarian Neoplasms (genetics, prevention & control)
• Ovariectomy
• Prospective Studies
• Risk Factors
• Risk Reduction Behavior
• Salpingostomy