Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Carey A. Cullinane, Jan Lubinski, Susan L. Neuhausen, Parviz Ghadirian, Henry T. Lynch, Claudine Isaacs, Barbara Weber, Pal Moller, Kenneth Offit, Charmaine Kim-Sing, Eitan Friedman, Susan Randall, Barbara Pasini, Peter Ainsworth, Ruth Gershoni-Baruch, William D. Foulkes, Jan Klijn, Nadine Tung, Gad Rennert, Olufunmilayo OlopadeFergus Couch, Teresa Wagner, Hakan Olsson, Ping Sun, Jeffrey N. Weitzel, Steven A. Narod

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCAl carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

Original languageEnglish
Pages (from-to)988-991
Number of pages4
JournalInternational Journal of Cancer
Volume117
Issue number6
DOIs
StatePublished - Dec 20 2005

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Breast Neoplasms
Pregnancy
Mutation
Odds Ratio
Confidence Intervals
Parturition
Parity
Reproductive History
Birth Order
Neoplasm Genes
Israel
Risk Reduction Behavior
North America
Case-Control Studies
Logistic Models

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Cullinane, C. A., Lubinski, J., Neuhausen, S. L., Ghadirian, P., Lynch, H. T., Isaacs, C., ... Narod, S. A. (2005). Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. International Journal of Cancer, 117(6), 988-991. https://doi.org/10.1002/ijc.21273

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. / Cullinane, Carey A.; Lubinski, Jan; Neuhausen, Susan L.; Ghadirian, Parviz; Lynch, Henry T.; Isaacs, Claudine; Weber, Barbara; Moller, Pal; Offit, Kenneth; Kim-Sing, Charmaine; Friedman, Eitan; Randall, Susan; Pasini, Barbara; Ainsworth, Peter; Gershoni-Baruch, Ruth; Foulkes, William D.; Klijn, Jan; Tung, Nadine; Rennert, Gad; Olopade, Olufunmilayo; Couch, Fergus; Wagner, Teresa; Olsson, Hakan; Sun, Ping; Weitzel, Jeffrey N.; Narod, Steven A.

In: International Journal of Cancer, Vol. 117, No. 6, 20.12.2005, p. 988-991.

Research output: Contribution to journalArticle

Cullinane, CA, Lubinski, J, Neuhausen, SL, Ghadirian, P, Lynch, HT, Isaacs, C, Weber, B, Moller, P, Offit, K, Kim-Sing, C, Friedman, E, Randall, S, Pasini, B, Ainsworth, P, Gershoni-Baruch, R, Foulkes, WD, Klijn, J, Tung, N, Rennert, G, Olopade, O, Couch, F, Wagner, T, Olsson, H, Sun, P, Weitzel, JN & Narod, SA 2005, 'Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers', International Journal of Cancer, vol. 117, no. 6, pp. 988-991. https://doi.org/10.1002/ijc.21273
Cullinane, Carey A. ; Lubinski, Jan ; Neuhausen, Susan L. ; Ghadirian, Parviz ; Lynch, Henry T. ; Isaacs, Claudine ; Weber, Barbara ; Moller, Pal ; Offit, Kenneth ; Kim-Sing, Charmaine ; Friedman, Eitan ; Randall, Susan ; Pasini, Barbara ; Ainsworth, Peter ; Gershoni-Baruch, Ruth ; Foulkes, William D. ; Klijn, Jan ; Tung, Nadine ; Rennert, Gad ; Olopade, Olufunmilayo ; Couch, Fergus ; Wagner, Teresa ; Olsson, Hakan ; Sun, Ping ; Weitzel, Jeffrey N. ; Narod, Steven A. / Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. In: International Journal of Cancer. 2005 ; Vol. 117, No. 6. pp. 988-991.
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abstract = "Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95{\%} confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95{\%} CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38{\%} decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95{\%} CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95{\%} CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17{\%} with each additional birth (OR = 1.17; 95{\%} CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95{\%} CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70{\%} compared to nulliparous controls (OR = 1.70; 95{\%} CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95{\%} CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCAl carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.",
author = "Cullinane, {Carey A.} and Jan Lubinski and Neuhausen, {Susan L.} and Parviz Ghadirian and Lynch, {Henry T.} and Claudine Isaacs and Barbara Weber and Pal Moller and Kenneth Offit and Charmaine Kim-Sing and Eitan Friedman and Susan Randall and Barbara Pasini and Peter Ainsworth and Ruth Gershoni-Baruch and Foulkes, {William D.} and Jan Klijn and Nadine Tung and Gad Rennert and Olufunmilayo Olopade and Fergus Couch and Teresa Wagner and Hakan Olsson and Ping Sun and Weitzel, {Jeffrey N.} and Narod, {Steven A.}",
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T1 - Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

AU - Cullinane, Carey A.

AU - Lubinski, Jan

AU - Neuhausen, Susan L.

AU - Ghadirian, Parviz

AU - Lynch, Henry T.

AU - Isaacs, Claudine

AU - Weber, Barbara

AU - Moller, Pal

AU - Offit, Kenneth

AU - Kim-Sing, Charmaine

AU - Friedman, Eitan

AU - Randall, Susan

AU - Pasini, Barbara

AU - Ainsworth, Peter

AU - Gershoni-Baruch, Ruth

AU - Foulkes, William D.

AU - Klijn, Jan

AU - Tung, Nadine

AU - Rennert, Gad

AU - Olopade, Olufunmilayo

AU - Couch, Fergus

AU - Wagner, Teresa

AU - Olsson, Hakan

AU - Sun, Ping

AU - Weitzel, Jeffrey N.

AU - Narod, Steven A.

PY - 2005/12/20

Y1 - 2005/12/20

N2 - Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCAl carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

AB - Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCAl carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

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