Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality

Susan M. Domchek, Tara M. Friebel, Christian F. Singer, D. Gareth Evans, Henry T. Lynch, Claudine Isaacs, Judy E. Garber, Susan L. Neuhausen, Ellen Matloff, Rosalind Eeles, Gabriella Pichert, Laura Van T'veer, Nadine Tung, Jeffrey N. Weitzel, Fergus J. Couch, Wendy S. Rubinstein, Patricia A. Ganz, Mary B. Daly, Olufunmilayo I. Olopade, Gail Tomlinson & 3 others Joellen Schildkraut, Joanne L. Blum, Timothy R. Rebbeck

Research output: Contribution to journalArticle

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Abstract

Context: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective: To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

Original languageEnglish
Pages (from-to)967-975
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume304
Issue number9
DOIs
StatePublished - Sep 1 2010

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Mutation
Breast Neoplasms
Mortality
Ovariectomy
Ovarian Neoplasms
Mastectomy
Neoplasms
Confidence Intervals
Genetic Research
Risk Reduction Behavior
North America
Multicenter Studies
Cohort Studies
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. / Domchek, Susan M.; Friebel, Tara M.; Singer, Christian F.; Gareth Evans, D.; Lynch, Henry T.; Isaacs, Claudine; Garber, Judy E.; Neuhausen, Susan L.; Matloff, Ellen; Eeles, Rosalind; Pichert, Gabriella; Van T'veer, Laura; Tung, Nadine; Weitzel, Jeffrey N.; Couch, Fergus J.; Rubinstein, Wendy S.; Ganz, Patricia A.; Daly, Mary B.; Olopade, Olufunmilayo I.; Tomlinson, Gail; Schildkraut, Joellen; Blum, Joanne L.; Rebbeck, Timothy R.

In: JAMA - Journal of the American Medical Association, Vol. 304, No. 9, 01.09.2010, p. 967-975.

Research output: Contribution to journalArticle

Domchek, SM, Friebel, TM, Singer, CF, Gareth Evans, D, Lynch, HT, Isaacs, C, Garber, JE, Neuhausen, SL, Matloff, E, Eeles, R, Pichert, G, Van T'veer, L, Tung, N, Weitzel, JN, Couch, FJ, Rubinstein, WS, Ganz, PA, Daly, MB, Olopade, OI, Tomlinson, G, Schildkraut, J, Blum, JL & Rebbeck, TR 2010, 'Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality', JAMA - Journal of the American Medical Association, vol. 304, no. 9, pp. 967-975. https://doi.org/10.1001/jama.2010.1237
Domchek, Susan M. ; Friebel, Tara M. ; Singer, Christian F. ; Gareth Evans, D. ; Lynch, Henry T. ; Isaacs, Claudine ; Garber, Judy E. ; Neuhausen, Susan L. ; Matloff, Ellen ; Eeles, Rosalind ; Pichert, Gabriella ; Van T'veer, Laura ; Tung, Nadine ; Weitzel, Jeffrey N. ; Couch, Fergus J. ; Rubinstein, Wendy S. ; Ganz, Patricia A. ; Daly, Mary B. ; Olopade, Olufunmilayo I. ; Tomlinson, Gail ; Schildkraut, Joellen ; Blum, Joanne L. ; Rebbeck, Timothy R. / Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. In: JAMA - Journal of the American Medical Association. 2010 ; Vol. 304, No. 9. pp. 967-975.
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title = "Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality",
abstract = "Context: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective: To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6{\%} vs 1{\%}, respectively; hazard ratio [HR], 0.14; 95{\%} confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6{\%} vs 2{\%}; HR, 0.28 [95{\%} CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20{\%} vs 14{\%}; HR, 0.63 [95{\%} CI, 0.41-0.96]) and BRCA2 mutation carriers (23{\%} vs 7{\%}; HR, 0.36 [95{\%} CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10{\%} vs 3{\%}; HR, 0.40 [95{\%} CI, 0.26-0.61]), breast cancer-specific mortality (6{\%} vs 2{\%}; HR, 0.44 [95{\%} CI, 0.26-0.76]), and ovarian cancer-specific mortality (3{\%} vs 0.4{\%}; HR, 0.21 [95{\%} CI, 0.06-0.80]). Conclusions: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.",
author = "Domchek, {Susan M.} and Friebel, {Tara M.} and Singer, {Christian F.} and {Gareth Evans}, D. and Lynch, {Henry T.} and Claudine Isaacs and Garber, {Judy E.} and Neuhausen, {Susan L.} and Ellen Matloff and Rosalind Eeles and Gabriella Pichert and {Van T'veer}, Laura and Nadine Tung and Weitzel, {Jeffrey N.} and Couch, {Fergus J.} and Rubinstein, {Wendy S.} and Ganz, {Patricia A.} and Daly, {Mary B.} and Olopade, {Olufunmilayo I.} and Gail Tomlinson and Joellen Schildkraut and Blum, {Joanne L.} and Rebbeck, {Timothy R.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1001/jama.2010.1237",
language = "English",
volume = "304",
pages = "967--975",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
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TY - JOUR

T1 - Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality

AU - Domchek, Susan M.

AU - Friebel, Tara M.

AU - Singer, Christian F.

AU - Gareth Evans, D.

AU - Lynch, Henry T.

AU - Isaacs, Claudine

AU - Garber, Judy E.

AU - Neuhausen, Susan L.

AU - Matloff, Ellen

AU - Eeles, Rosalind

AU - Pichert, Gabriella

AU - Van T'veer, Laura

AU - Tung, Nadine

AU - Weitzel, Jeffrey N.

AU - Couch, Fergus J.

AU - Rubinstein, Wendy S.

AU - Ganz, Patricia A.

AU - Daly, Mary B.

AU - Olopade, Olufunmilayo I.

AU - Tomlinson, Gail

AU - Schildkraut, Joellen

AU - Blum, Joanne L.

AU - Rebbeck, Timothy R.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Context: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective: To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

AB - Context: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective: To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

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DO - 10.1001/jama.2010.1237

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JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

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