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

H. Jernström, C. Lerman, P. Ghadirian, Henry T. Lynch, B. Weber, J. Garber, M. Daly, O. I. Olopade, W. D. Foulkes, E. Warner, J. S. Brunet, S. A. Narod

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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.

Original languageEnglish
Pages (from-to)1846-1850
Number of pages5
JournalThe Lancet
Volume354
Issue number9193
DOIs
StatePublished - Nov 27 1999

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Breast Neoplasms
Pregnancy
Parturition
Mutation
Birth Order
Germ-Line Mutation
Mastectomy
Genetic Counseling
Ovariectomy
Pregnancy Outcome
Parity
Hysterectomy
Ovarian Neoplasms
Case-Control Studies
Odds Ratio
Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Jernström, H., Lerman, C., Ghadirian, P., Lynch, H. T., Weber, B., Garber, J., ... Narod, S. A. (1999). Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. The Lancet, 354(9193), 1846-1850. https://doi.org/10.1016/S0140-6736(99)04336-6

Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. / Jernström, H.; Lerman, C.; Ghadirian, P.; Lynch, Henry T.; Weber, B.; Garber, J.; Daly, M.; Olopade, O. I.; Foulkes, W. D.; Warner, E.; Brunet, J. S.; Narod, S. A.

In: The Lancet, Vol. 354, No. 9193, 27.11.1999, p. 1846-1850.

Research output: Contribution to journalArticle

Jernström, H, Lerman, C, Ghadirian, P, Lynch, HT, Weber, B, Garber, J, Daly, M, Olopade, OI, Foulkes, WD, Warner, E, Brunet, JS & Narod, SA 1999, 'Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2', The Lancet, vol. 354, no. 9193, pp. 1846-1850. https://doi.org/10.1016/S0140-6736(99)04336-6
Jernström H, Lerman C, Ghadirian P, Lynch HT, Weber B, Garber J et al. Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. The Lancet. 1999 Nov 27;354(9193):1846-1850. https://doi.org/10.1016/S0140-6736(99)04336-6
Jernström, H. ; Lerman, C. ; Ghadirian, P. ; Lynch, Henry T. ; Weber, B. ; Garber, J. ; Daly, M. ; Olopade, O. I. ; Foulkes, W. D. ; Warner, E. ; Brunet, J. S. ; Narod, S. A. / Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. In: The Lancet. 1999 ; Vol. 354, No. 9193. pp. 1846-1850.
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title = "Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2",
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.",
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T1 - Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2

AU - Jernström, H.

AU - Lerman, C.

AU - Ghadirian, P.

AU - Lynch, Henry T.

AU - Weber, B.

AU - Garber, J.

AU - Daly, M.

AU - Olopade, O. I.

AU - Foulkes, W. D.

AU - Warner, E.

AU - Brunet, J. S.

AU - Narod, S. A.

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Y1 - 1999/11/27

N2 - 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.

AB - 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.

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