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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)306-313
Number of pages8
JournalJAMA oncology
Volume1
Issue number3
DOIs
StatePublished - Jun 1 2015

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Ovariectomy
Breast Neoplasms
Mutation
Survival
Estrogen Receptors
Ovarian Neoplasms
BRCA2 Gene
BRCA1 Gene
Second Primary Neoplasms
Mortality
Germ-Line Mutation
Pedigree
Counseling
Ovary

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Metcalfe, K., Lynch, H. T., Foulkes, W. D., Tung, N., Kim-Sing, C., Olopade, O. I., ... Narod, S. A. (2015). Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. JAMA oncology, 1(3), 306-313. https://doi.org/10.1001/jamaoncol.2015.0658

Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. / Metcalfe, Kelly; Lynch, Henry T.; Foulkes, William D.; Tung, Nadine; Kim-Sing, Charmaine; Olopade, Olufunmilayo I.; Eisen, Andrea; Rosen, Barry; Snyder, Carrie; Gershman, Shelley; Sun, Ping; Narod, Steven A.

In: JAMA oncology, Vol. 1, No. 3, 01.06.2015, p. 306-313.

Research output: Contribution to journalArticle

Metcalfe, K, Lynch, HT, Foulkes, WD, Tung, N, Kim-Sing, C, Olopade, OI, Eisen, A, Rosen, B, Snyder, C, Gershman, S, Sun, P & Narod, SA 2015, 'Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers', JAMA oncology, vol. 1, no. 3, pp. 306-313. https://doi.org/10.1001/jamaoncol.2015.0658
Metcalfe, Kelly ; Lynch, Henry T. ; Foulkes, William D. ; Tung, Nadine ; Kim-Sing, Charmaine ; Olopade, Olufunmilayo I. ; Eisen, Andrea ; Rosen, Barry ; Snyder, Carrie ; Gershman, Shelley ; Sun, Ping ; Narod, Steven A. / Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. In: JAMA oncology. 2015 ; Vol. 1, No. 3. pp. 306-313.
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AU - Metcalfe, Kelly

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AU - Kim-Sing, Charmaine

AU - Olopade, Olufunmilayo I.

AU - Eisen, Andrea

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N2 - 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.

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