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Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2

Jernström, Helena LU ; Lerman, C ; Ghadirian, P ; Lynch, H T ; Weber, B ; Garber, J ; Daly, M ; Olopade, O I ; Foulkes, W D and Warner, E , et al. (1999) In The Lancet 354(9193). p.1846-1850
Abstract
BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who... (More)
BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. FINDINGS: A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. INTERPRETATION: Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet
volume
354
issue
9193
pages
1846 - 1850
publisher
Elsevier
external identifiers
  • pmid:10584720
  • scopus:0033610723
ISSN
1474-547X
DOI
10.1016/S0140-6736(99)04336-6
language
English
LU publication?
yes
id
a57c2e1a-c8f1-4551-b3dd-c1a92e34aeac (old id 1114639)
date added to LUP
2016-04-01 12:21:54
date last changed
2022-04-21 06:10:41
@article{a57c2e1a-c8f1-4551-b3dd-c1a92e34aeac,
  abstract     = {{BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. FINDINGS: A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. INTERPRETATION: Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.}},
  author       = {{Jernström, Helena and Lerman, C and Ghadirian, P and Lynch, H T and Weber, B and Garber, J and Daly, M and Olopade, O I and Foulkes, W D and Warner, E and Brunet, J S and Narod, S A}},
  issn         = {{1474-547X}},
  language     = {{eng}},
  number       = {{9193}},
  pages        = {{1846--1850}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2}},
  url          = {{http://dx.doi.org/10.1016/S0140-6736(99)04336-6}},
  doi          = {{10.1016/S0140-6736(99)04336-6}},
  volume       = {{354}},
  year         = {{1999}},
}