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

Cullinane, CA; Lubinski, J; Neuhausen, SL; Ghadirian, P; Lynch, HT; Isaacs, C; Weber, B; Moller, P; Offit, K and Kim-Sing, C, et al. (2005) In International Journal of Cancer 117(6). p.988-991
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... (More)
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 BRCA1 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. (Less)
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published
subject
keywords
BRCA mutation, parity, breast cancer
in
International Journal of Cancer
volume
117
issue
6
pages
988 - 991
publisher
John Wiley & Sons
external identifiers
  • pmid:15986445
  • wos:000233384900014
  • scopus:28044451561
ISSN
0020-7136
DOI
10.1002/ijc.21273
language
English
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yes
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bc2d2e58-3cdb-48e1-b1d6-347b9601c4c6 (old id 212189)
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2007-08-10 11:18:31
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2017-10-22 03:41:54
@article{bc2d2e58-3cdb-48e1-b1d6-347b9601c4c6,
  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 BRCA1 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, CA and Lubinski, J and Neuhausen, SL and Ghadirian, P and Lynch, HT and Isaacs, C and Weber, B and Moller, P and Offit, K and Kim-Sing, C and Friedman, E and Randall, S and Pasini, B and Ainsworth, P and Gershoni-Baruch, R and Foulkes, WD and Klijn, J and Tung, N and Rennert, G and Olopade, O and Couch, F and Wagner, T and Olsson, Håkan and Sun, P and Weitzel, JN and Narod, SA},
  issn         = {0020-7136},
  keyword      = {BRCA mutation,parity,breast cancer},
  language     = {eng},
  number       = {6},
  pages        = {988--991},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1002/ijc.21273},
  volume       = {117},
  year         = {2005},
}