Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers.

Abstract

IMPORTANCE:

Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face a lifetime risk of breast cancer of up to 70%, and once they receive a diagnosis of breast cancer, they face high risks of both second primary breast and ovarian cancers. Preventive bilateral salpingo-oophorectomy is recommended to women with a BRCA mutation at age 35 years or thereafter to prevent breast and ovarian cancer, but it is unclear whether oophorectomy has an impact on survival in women with BRCA-associated breast cancer.

OBJECTIVE:

To estimate the impact of oophorectomy on survival in women with breast cancer with a BRCA1 or BRCA2 mutation.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective analysis of patients selected by pedigree review of families who received counseling at 1 of 12 participating clinical genetics centers. Patients were 676 women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation who were observed for up to 20 years after receiving a diagnosis between 1975 and 2008. Survival experience was compared for women who did and who did not undergo oophorectomy.

MAIN OUTCOMES AND MEASURES:

In all analyses, the primary end point was death due to breast cancer.

RESULTS:

Of the 676 women, 345 underwent oophorectomy after the diagnosis of breast cancer and 331 retained both ovaries. The 20-year survival for the entire patient cohort was 77.4%. The adjusted hazard ratio for death attributed to breast cancer in women who underwent oophorectomy was 0.38 (95% CI, 0.19-0.77; P = .007) for BRCA1 carriers and 0.57 (95% CI, 0.23-1.43; P = .23) for BRCA2 carriers. The hazard ratio for breast cancer-specific mortality was 0.76 (95% CI, 0.32-1.78; P = .53) for women with estrogen receptor-positive breast cancer and 0.07 (95% CI, 0.01-0.51; P = .009) for women with estrogen receptor-negative breast cancer.

CONCLUSIONS AND RELEVANCE:

Oophorectomy is associated with a decrease in mortality in women with breast cancer and a BRCA1 mutation. Women with estrogen receptor-negative breast cancer and a BRCA1 mutation should undergo oophorectomy shortly after diagnosis.

• Authors: Kelly Metcalfe, Henry T Lynch, William D Foulkes, Nadine Tung, Charmaine Kim-Sing, Olufunmilayo I Olopade, Andrea Eisen, Barry Rosen, Carrie Snyder, Shelley Gershman, Ping Sun, Steven A Narod
• Journal: JAMA oncology (JAMA Oncol) Vol. 1 Issue 3 Pg. 306-13 (Jun 2015) ISSN: 2374-2445 [Electronic] United States
• PMID: 26181175 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Biomarkers, Tumor

Topics

• Adult
• Aged
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (genetics, mortality, pathology, therapy)
• Canada
• Chi-Square Distribution
• DNA Mutational Analysis
• Female
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• Middle Aged
• Ovarian Neoplasms (genetics, mortality, pathology, prevention & control)
• Ovariectomy (adverse effects, mortality)
• Phenotype
• Proportional Hazards Models
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome
• United States
• Young Adult