Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers

Timothy R. Rebbeck, Albert M. Levin, Andrea Eisen, Carrie Snyder, Patrice Watson, Lisa Cannon-Albright, Claudine Isaacs, Olofunmilayo Olopade, Judy E. Garber, Andrew K. Godwin, Mary B. Daly, Steven A. Narod, Susan L. Neuhausen, Henry T. Lynch, Barbara L. Weber

Research output: Contribution to journalArticle

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Abstract

Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33- 0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12- 0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

Original languageEnglish
Pages (from-to)1475-1479
Number of pages5
JournalJournal of the National Cancer Institute
Volume91
Issue number17
StatePublished - Sep 1 1999

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Ovariectomy
Breast Neoplasms
Mutation
Ovarian Neoplasms
Confidence Intervals
Birthing Centers
Hormones
BRCA1 Gene
Germ-Line Mutation
Hormone Replacement Therapy
Genetic Testing
Risk Reduction Behavior
Ovary
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Rebbeck, T. R., Levin, A. M., Eisen, A., Snyder, C., Watson, P., Cannon-Albright, L., ... Weber, B. L. (1999). Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. Journal of the National Cancer Institute, 91(17), 1475-1479.

Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. / Rebbeck, Timothy R.; Levin, Albert M.; Eisen, Andrea; Snyder, Carrie; Watson, Patrice; Cannon-Albright, Lisa; Isaacs, Claudine; Olopade, Olofunmilayo; Garber, Judy E.; Godwin, Andrew K.; Daly, Mary B.; Narod, Steven A.; Neuhausen, Susan L.; Lynch, Henry T.; Weber, Barbara L.

In: Journal of the National Cancer Institute, Vol. 91, No. 17, 01.09.1999, p. 1475-1479.

Research output: Contribution to journalArticle

Rebbeck, TR, Levin, AM, Eisen, A, Snyder, C, Watson, P, Cannon-Albright, L, Isaacs, C, Olopade, O, Garber, JE, Godwin, AK, Daly, MB, Narod, SA, Neuhausen, SL, Lynch, HT & Weber, BL 1999, 'Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers', Journal of the National Cancer Institute, vol. 91, no. 17, pp. 1475-1479.
Rebbeck TR, Levin AM, Eisen A, Snyder C, Watson P, Cannon-Albright L et al. Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. Journal of the National Cancer Institute. 1999 Sep 1;91(17):1475-1479.
Rebbeck, Timothy R. ; Levin, Albert M. ; Eisen, Andrea ; Snyder, Carrie ; Watson, Patrice ; Cannon-Albright, Lisa ; Isaacs, Claudine ; Olopade, Olofunmilayo ; Garber, Judy E. ; Godwin, Andrew K. ; Daly, Mary B. ; Narod, Steven A. ; Neuhausen, Susan L. ; Lynch, Henry T. ; Weber, Barbara L. / Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 17. pp. 1475-1479.
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abstract = "Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95{\%} confidence interval [CI] = 0.33- 0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95{\%} CI = 0.08-0.94) or at least 10 (HR = 0.33; 95{\%} CI = 0.12- 0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.",
author = "Rebbeck, {Timothy R.} and Levin, {Albert M.} and Andrea Eisen and Carrie Snyder and Patrice Watson and Lisa Cannon-Albright and Claudine Isaacs and Olofunmilayo Olopade and Garber, {Judy E.} and Godwin, {Andrew K.} and Daly, {Mary B.} and Narod, {Steven A.} and Neuhausen, {Susan L.} and Lynch, {Henry T.} and Weber, {Barbara L.}",
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T1 - Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers

AU - Rebbeck, Timothy R.

AU - Levin, Albert M.

AU - Eisen, Andrea

AU - Snyder, Carrie

AU - Watson, Patrice

AU - Cannon-Albright, Lisa

AU - Isaacs, Claudine

AU - Olopade, Olofunmilayo

AU - Garber, Judy E.

AU - Godwin, Andrew K.

AU - Daly, Mary B.

AU - Narod, Steven A.

AU - Neuhausen, Susan L.

AU - Lynch, Henry T.

AU - Weber, Barbara L.

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N2 - Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33- 0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12- 0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

AB - Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33- 0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12- 0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

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