Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Joanne Kotsopoulos, Jan Lubinski, Henry T. Lynch, Charmaine Kim-Sing, Susan Neuhausen, Rochelle Demsky, William D. Foulkes, Parviz Ghadirian, Nadine Tung, Peter Ainsworth, Leigha Senter, Beth Karlan, Andrea Eisen, Charis Eng, Jeffrey Weitzel, Dawna M. Gilchrist, Joanne L. Blum, Dana Zakalik, Christian Singer, Taya Fallen & 4 others Ophira Ginsburg, Tomasz Huzarski, Ping Sun, Steven A. Narod

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Abstract

Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. Methods: We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ =-0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend <0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; Ptrend <0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006). Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.

Original languageEnglish
Pages (from-to)1089-1096
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number7
DOIs
StatePublished - Jul 2012

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Ovariectomy
Menopause
Breast Neoplasms
Mutation
Confidence Intervals
Menarche
Chemoprevention
Breast Feeding
Case-Control Studies
Cohort Studies
Logistic Models
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. / Kotsopoulos, Joanne; Lubinski, Jan; Lynch, Henry T.; Kim-Sing, Charmaine; Neuhausen, Susan; Demsky, Rochelle; Foulkes, William D.; Ghadirian, Parviz; Tung, Nadine; Ainsworth, Peter; Senter, Leigha; Karlan, Beth; Eisen, Andrea; Eng, Charis; Weitzel, Jeffrey; Gilchrist, Dawna M.; Blum, Joanne L.; Zakalik, Dana; Singer, Christian; Fallen, Taya; Ginsburg, Ophira; Huzarski, Tomasz; Sun, Ping; Narod, Steven A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 7, 07.2012, p. 1089-1096.

Research output: Contribution to journalArticle

Kotsopoulos, J, Lubinski, J, Lynch, HT, Kim-Sing, C, Neuhausen, S, Demsky, R, Foulkes, WD, Ghadirian, P, Tung, N, Ainsworth, P, Senter, L, Karlan, B, Eisen, A, Eng, C, Weitzel, J, Gilchrist, DM, Blum, JL, Zakalik, D, Singer, C, Fallen, T, Ginsburg, O, Huzarski, T, Sun, P & Narod, SA 2012, 'Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 7, pp. 1089-1096. https://doi.org/10.1158/1055-9965.EPI-12-0201
Kotsopoulos, Joanne ; Lubinski, Jan ; Lynch, Henry T. ; Kim-Sing, Charmaine ; Neuhausen, Susan ; Demsky, Rochelle ; Foulkes, William D. ; Ghadirian, Parviz ; Tung, Nadine ; Ainsworth, Peter ; Senter, Leigha ; Karlan, Beth ; Eisen, Andrea ; Eng, Charis ; Weitzel, Jeffrey ; Gilchrist, Dawna M. ; Blum, Joanne L. ; Zakalik, Dana ; Singer, Christian ; Fallen, Taya ; Ginsburg, Ophira ; Huzarski, Tomasz ; Sun, Ping ; Narod, Steven A. / Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 7. pp. 1089-1096.
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abstract = "Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. Methods: We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ =-0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend <0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95{\%} confidence interval (CI), 0.40-0.66; Ptrend <0.0001] was greater than that associated with natural menopause (OR, 0.81; 95{\%} CI, 0.62-1.07; P trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95{\%} CI, 0.02-0.54; P = 0.006). Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.",
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T1 - Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

AU - Kotsopoulos, Joanne

AU - Lubinski, Jan

AU - Lynch, Henry T.

AU - Kim-Sing, Charmaine

AU - Neuhausen, Susan

AU - Demsky, Rochelle

AU - Foulkes, William D.

AU - Ghadirian, Parviz

AU - Tung, Nadine

AU - Ainsworth, Peter

AU - Senter, Leigha

AU - Karlan, Beth

AU - Eisen, Andrea

AU - Eng, Charis

AU - Weitzel, Jeffrey

AU - Gilchrist, Dawna M.

AU - Blum, Joanne L.

AU - Zakalik, Dana

AU - Singer, Christian

AU - Fallen, Taya

AU - Ginsburg, Ophira

AU - Huzarski, Tomasz

AU - Sun, Ping

AU - Narod, Steven A.

PY - 2012/7

Y1 - 2012/7

N2 - Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. Methods: We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ =-0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend <0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; Ptrend <0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006). Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.

AB - Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. Methods: We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ =-0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend <0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; Ptrend <0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006). Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.

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